- Email: [email protected]
Acceptability of injectable contraceptives in Assiut, Egypt
CONTRACEPTION
ACCEPTABILITY
OF INJECTABLE
CONTRACEPTIVES
IN ASSIUT,
EGYPT
H.T. Salem*, M. Salah, M.Y. Aly, A.I. Thabet, M.M. Shaaban and M.F. Fathalla
Department
of Obstetrics and Gynaecology Assiut, Egypt
Abstract The present work was a randomized comparative study of two injectable progestogen-only contraceptives. The first (200 subjects) received 150 of depotgroup medroxyprogesterone acetate (Depoprovera) t:ery 8427 days and the second (200 subjects) received 200 mg of norethisterone enanthate (Noristerat) every 56+7 days. Acceptors of injectable contraceptives in Assiut, Egypt, were mainly women looking for fertility termination. Menstrual disruption was the main side effect among both treatment groups. Amenorrhoea was the commonest menstrual complaint and was the main reason for discontinuation in both groups. Only one pregnancy occurred during NET-EN use; two more pregnancies occurred, one in each of the two groups but there were indications that conception preceded the first injection. Menstrual irregularities were generally more frequent with DMPA users. However, DMPA had better rates one-year continuation than NET-EN (68.823.5 and 57.1r3.6 per 100 women, respectively).
*To whom correspondence
should be addressed.
Submitted for publication March 31, 1987 Accepted for publication September 15, 1988
DECEMBER
1988 VOL. 38 NO. 6
697
CONTRACEPTION
Introduction Injectable contraceptives have now been in use for over two decades in some 80 countries and by over 10 million women. In Egypt they have been used only on a limited scale and for research purposes (l-3). Injectable contraceptives have the advantages of being very effective methods and require administration every two or three months (l-7). The idea of long-acting contraceptives is welcomed by Egyptian women (8). This has prompted studying the use of injectable contraceptives in different parts of Egypt. In the present study we have conducted a randomized comparative field trial in the use of depot-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN) in Assiut, Egypt, to evaluate the performance of the two injectables in the community as regards side effects, continuation and terminations. The hypothesis is that the menstrual performance of the two preparations might differ in a way that influences continuation rates. Material
and Method
Four-hundred women were recruited from among those attending the El-Welledia Family Planning Center in Assiut, Based on a random table, 200 women started use of Egypt. Randomization table was DMPA and 200 started use of NET-EN. prepared by the WHO, Special Programme of Research, in Human Reproduction. Development and Research Training The women were allocated by picking a seated envelope which had a number that assigned her to one of the two methods. Before they were accepted into the study, all women underwent a physical examination and were given information about the method to be used and the possible side effects. The inclusion criteria were: - Age between 18 and 40 years. - Women with proven fertility and with frequent exposure to the risk of pregnancy. - Regular menstrual cycles. - Willingness to rely only upon this method. - Willingness and ability to return at the scheduled follow-up visits. The exclusion
criteria
were:
-
Breast-feeding. Present or past cardiovascular disease. Present or past liver disease. Known or suspected breast malignancy. Known or suspected genital malignancy or uterine fibroids. - Undiagnosed vaginal bleeding. - Suspected pregnancy.
698
DECEMBER
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CONTRACEPTION
The regimen used for DMPA was 150 mg given by deep I.M. injection every three months and that for NET-EN was 200 mg for one year. At each scheduled I.M. every two months visit, spontaneous complaints were recorded together with the details of menstrual changes, blood pressure, weight and These were date of physical examination. recorded on WHO special records designed by Special Programme of Development and Research Training in Research, Human Reproduction. No list of complications was read to the users. Women who complained of heavy and/or prolonged bleeding were first examined to exclude possible gynaecological lesions and were evaluated for anaemia and given iron supplements accordingly. If bleeding persisted, the subject was referred for D&C biopsy and was excluded from the study. For women who had no menstruation for at least 8 weeks during the first 6 months of treatment, pregnancy was excluded by pelvic examination, pregnancy test and ultrasonography.
Results Table I gives the characteristics of the acceptors. The mean ages of DMPA and NET-EN users were 32.4 and 33.1, respectively, with women 35 years or more representing more than half of each group. The mean parity of DMPA users was 6.4, and 69.5% of the women had 5 or more previous deliveries. The mean parity of NET-EN users was 6.6, and 80.5% of the women had 5 or more previous deliveries. About 54.5% of DMPA users were from urban areas, while 45.5 were from rural areas. For NET-EN the percentages were equal. The outcome of last pregnancy was live-birth in 94% of DMPA users and 93% of NET-EN users. About two-thirds of acceptors of both methods had been currently using other methods of contraception prior to admission to the study. Oral contraceptives represented the most commonly used method (90%). Menstrual complaints among DMPA users are given in Table II and Figure 1. While 37.3% reported no menstrual problem 3 months after using DMPA, 27.1% of those who came to the la-month follow-up (107 women) had no complaints. Amenorrhoea was reported most frequently with its incidence increasing with time (from 30.8% after 3 months to 55.1% by the end of the year). The other menstrual complaints such as irregular bleeding, spotting, heavy bleeding and oligohypomenorrhoea and/or hypomenorrhoea generally tended to remain steady or diminish in those women who continued to use the method up until the end of the first year.
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CONTRACEPTION
Table I :
Religion
and socio-demographic
characteristics
of the acceptors
DMPA
NET-EN
No.
%
No.
%
153 47
76.5% 23.5?6
161 39
80.5% 19.5%
Urban* Rural
109 91
54.5% 45.5%
100 100
50.0% 50.0%
20 25 30 35
14 38 4G 102
7.0?$ 19.0% 23.0% 51.0%
5 35 55 105
2.5% 17.5% 27.5% 52.5%
:
- Religion
Moslems Christians
:
- Residence
- Age : -
24 29 34 39
- Mean age -+ S.D. - Parity : l-2 3-4 5-6 7-6 9 - Mean parity * By urban
+ S.D.
area
is meant
32.4 + 5.7 12 49 46 49 44
33.1 + 5.0 4 35 60 60 41
6.0% 24.5% 23.0% 24.596 22.0% 6.2 -+ 2.9
the governorate
capital
Table II : Incidence of menstrual complaints months after acceptance (?b)
6.6 + 2.3 and main cities.
among
DMPA
users
by
Months after
acceptance
(n=F21)
(n=9107)
(n=11207)
33 (30.8?&)
(27?%)
41 (33.9%)
50 (46.8%)
59 (55.1%)
13??$
17 (15.9?9
( 91&x,
( 5.i%)
( 3.:w1
3 ( 2.0%)
( A)
( 1.9%)
None Amenorrtoea Irregular
2.0% 17.5% 30.0% 30.0?6 20.5%
bleeding
Spotting Heavy bleeding Oligomenorrhoea hypomenorrhoea
700
and/or
2 3 (2.5%)
DECEMBER
1 ( 0.9%)
1988 VOL. 38 NO. 6
CONTRACEPTION
Irreg. bl. +.-spot. \,
_
_
_e+-
-
d
. .
---=--y.
H.bl.3 3
6
Duration
Figure 1:
-
9
_h12
(months)
Menstrual
problems
acceptors
during one year of use
reported by DMPA
None = No menstrual abnormalities Irreg. bl. = Irregular bleeding H. bl. = Heavy bleeding Am. = Amenorrhoea spot. = Spotting
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1988 VOL. 38 NO. 6
701
CONTRACEPTION
Table III:
Incidence of menstrual complaints months after acceptance (%)
among NET-EN users by
Months after --(n=l256) None
(n=143I)
(n=FIl)
84 66 64 (53.996) (50.436) (57.S)
acceptance (n=YOl)
(n=l”,4)
(464k)
(333k)
(302&J
(3&)
(421&b)
Amenorrhoea (18296%) (2&) Irregular bleeding
(27??&) (323k)
7 17 12 ( 6.396) (11.996) (18.1?6)
(l6tko) 2
Spotting
( 2.lS) Heavy bleeding
( Z.f?&) Oligomenorrhoea and/or hypomenorrhoea ( 5.796) ( 6.196) ( 1.876) ( l.OS) ( 0.096) ( 6.k)
Menstrual complaints among NET-EN users are shown in Table III and Figure 2. While 53.9% reported no menstrual problem 2 months after using NET-EN, 30.9% had no menstrual complaints at the end of the year. Amenorrhoea was reported most frequently with its incidence increasing with time (from 18.6 at 2 months to 42.5% by the end of the year). Irregular bleeding was reported next in frequency with its incidence increasing with time. Complaints of oligohypomenorrhoea and/or hypomenorrhoea also slightly increased with time. Only complaints of spotting and heavy bleeding diminished with time. Among DMPA users, headache was reported most frequently with its incidence slightly increasing with time (from 11.6% at 3 months to 15% at the end of the year). Next in frequency and with increasing incidence were abdominal distension and low backache. The incidence of the vague complaint of general weakness diminished with time, reaching 3.7% by the end of the year. Lower abdominal distension was reported by only 1.9% at the end of the year. Partial hair loss was reported by only 1.9% at 9 months and by 2.8% by the end of the year.
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CONTRACEPTION
% 70
60
50
40
30
20 Irreg.bl.&
-
- -?,
10
,
.X'
.
Duration
Figure 2:
P---___
.,.
(months)
Menstrual
problems
reported by NET-EN
acceptors
during one year of use.
None = No menstrual abnormalities Irreg. bl. = Irregular bleeding H. bl. = Heavy bleeding Am. = Amenorrhoea spot. = Spotting
DECEMBER
1988 VOL. 38 NO. 6
703
46
57
-
NET-EN
- DMPA
Decrease
28.0
la.1
30
17
- NET-EN
60.6
43.0
- DMPA
- No change
-
29.0
21.3
31
20
%
- DhlPA
No.
5-40
5-35
S-20
5-35
Range
Systolic
i6.a+a.a
13.7+7.3
lo.az5.4
13.2ta.3
Mean+S.D.
28.9 23.4
31 22
53.3 59.6
51 56
17.8 17.0
16
%
19
No.
Blood Pressure
S-20
5-20
5-20
S-30
Range
Diastolic
9.4 6.4
l-l.!
6
1-a
16.8
1-21
21.3
l-20
72.3
Rnnge
73.8
. 90
10
la 20
9.~~4.0
68
lO.dz5.1
79
9.024.9
No.
10.5L6.6
b1ean~S.D.
Keight
Classification of DMPA and NET-EN users at the end of the study according to net changes in blood pressure and weight
- NET-EN
- Increase
Table IV:
3.423.0
3.6z1.9
4.723.3
5.5+3.9 _
Mcnn+S.D.
CONTRACEPTION
Table V:
One-year cumulative termination and continuationrates per 100 acceptors,and events,firstsegment of use Rates DMPA
Pregnancy Bleeding Amenorrhoea Other medical Other personal Planning pregnancy Total termination Continuation Lost to follow-up Women-years of use
0.5+0-s 8.172.1 10.672.3 2.271.1 3.671.4 6.371.8 31.3T3.5 68.873.5 l?i6
Events NET-EN
1.0+0.7 12.572.4 13.072.5 5.971.7 4.471.5 6.171.8 42.973.6 57.173.6 13T50
* Faulty selection was most probably pregnancy in each treatment group.
DMPA
NET-EN
1* 14 19 4 6 11 55 107 145.7
2* 23 24 11 8 11 7s 34 139.6
the cause of one
reported was most users, headache NET-EN Among increasing with time (from frequently with its incidence The 3.2% at 3 months to 19.4% by the end of the year). distension abdominal low backache and incidences of by increased with time, reaching 5.3 and 3.2, respectively, The incidence of the vague complaint the end of the year. of general weakness diminished with time, reaching 5.3% by the end of the year. Table IV gives the changes in blood pressure and weight BY the end of the year, there among DMPA and NET-EN users. was a statistically significant decrease in the systolic and for both DMPA and NET-EN users. diastolic blood pressures The percentage of users who showed a decrease in systolic and diastolic blood pressures was higher among the NET-EN group than among the DMPA group (61% for the systolic and 60% for the diastolic in the NET-EN group versus 43 and 53 in the DMPA group). There was a statistically insignificant increase in the mean body weight of acceptors of both DMPA and NET-EN. About three-fourths of each group showed an increase in body weight. The reasons for terminations are shown by the lifeOne pregnancy was table rates and events in Table V. detected among DMPA users and two among NET-EN users. However, judging from the duration of pregnancy at the first one pregnancy in each group was due to faulty follow-up,
DECEMBER
1988 VOL. 38 NO. 6
705
CONTRACEPTION
This resulted from selection rather than method failure. the women giving false data about the date of their last The outcome of pregnancies was two males and menstruation. one female who were healthy with no apparent abnormalities. The two most important causes of discontinuation among both groups of contraceptive users were amenorrhoea and for 19 Amenorrhoea accounted bleeding problems. terminations among DMPA users with a net rate of 10.6 per 100 women at one year and for 24 terminations among NET-EN users with a net rate of 13.0 per 100 women at one year. Bleeding problems accounted for 14 terminations among DMPA users and 23 terminations among NET-EN users with net rates of 8.1 and 12.5 per 100 women, respectively. The one-year continuation rates were 68.8 and 57.1 per 100 women for the DMPA and NET-EN groups, respectively. Discussion injectable acceptors of study the In the present for fertility women looking were mostly contraceptives termination rather than for spacing: most of the subjects were relatively older (mean ages 32 and 33 years) and of high parity (mean parity 6.6 and 6.4) for DMPA and NET-EN, The age and parity of injectable acceptors respectively. are comparable to those of implant acceptors in the same locality (8). Menstrual disruptions were the main side effects among both treatment groups and generally were more common with DMPA than NET-EN users. Amenorrhoea was the most frequent menstrual complaint and was more frequent with DMPA, and its incidence increased with time. At the end of one year, 55% and 42.5% of DMPA and NET-EN acceptors, respectively, were amenorrhoeic. A WHO multicentre clinical trial (6) reported that by the end of one year use of DMPA, 35% of acceptors became amenorrhoeic and that the incidence of amenorrhoea increased with duration of use. With NET-EN users the incidence of amenorrhoea after one year of use was reported to be lo-25% (3,9), a much lower incidence than that found in the present study. Bleeding was also more common with DMPA than with NET-EN (31.5% and 27.5%, respectively) at the first follow-up visit. However, by the end of one year, there was a decrease in the incidence of bleeding among both treatment groups. Headache was the most common non-menstrual complaint and was more frequent among DMPA users. It was time related and its incidence increased with prolonged use. Other studies also showed that headache was reported as the most common non-menstrual complaint of women using injectable contraceptives (6,10,11).
706
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1988 VOL. 38 NO. 6
CONTRACEPTION
but With both treatment groups there was a slight, in the mean systolic and diastolic significant, decrease blood pressures which was more apparent with the NET-EN Most studies have reported insignificant changes acceptors. in women using in systolic and diastolic blood pressure either DMPA or NET-EN (6,7,12-14). After one year of use there was an insignificant in the mean body weight of acceptors of both increase groups. Weight gain was welcomed by most Egyptian women, especially in rural areas. A similar observation was reported in the Philippines (15). The one-year continuation rates for DMPA and NET-EN These were 68.8 and 57.1 per 100 women-years, respectively. rates are lower than the respective rates reported by the first WHO multicentre study (5) which were 71.2 and 75.6, but higher than those reported by the second WHO clinical trial (16), 48.6 and 50 per 100 women-years, respectively. The main cause of discontinuation was amenorrhoea (10.6 and 13 per 100 women for DMPA and NET-EN, respectively). Although amenorrhoea was more common among DMPA users, the discontinuation for amenorrhoea was higher for NET-EN users. The more convenient 3-monthly regimen of DMPA is a possible explanation. Culturally, especially in rural areas, amenorrhoea is regarded as a sign of ill health as menstruation is essential to get rid of "bad bloodS1 which causes headache, lethargy, abdominal distension and a sense of general ill health. Furthermore, amenorrhoea creates in some women a fear of pregnancy, infertility, menopause or onset of senility. Bleeding was the next common cause of discontinuation (8.1 and 12.5 per 100 women-years for DMPA and NET-EN, respectively). The discontinuation rate for DMPA is than bleeding irregularities for lower those reported by WHO (9.3 and 15.1 per 100 women-years) (5,16). The majority of the population in our locality are Moslems and these bleeding problems are poorly tolerated as they duties such as praying and will interfere with religious Ramadan fasting besides interfering with sexual activities. Three cases of pregnancy occurred during this study (one with DMPA and two with NET-EN). In fact, fault of selection was the cause of one pregnancy in each treatment group, as they received the first injection too late after menstruation. The pregnancy rate for DMPA in the present study is similar to other studies using the same dosage regimen With NET-EN, the pregnancy rate in this study is (5,6,17). similar to that reported by the WHO multicentre also
DECEMBER
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CONTRACEPTION
clinical trial (16) using NET-EN in a regimen of 200 mg every 8 weeks throughout the study. Unacceptably higher pregnancy rates have been reported when NET-EN injection was given every 12 weeks after the first 4 injections (18).
Conclusions Injectable contraceptives (DMPA and NET-EN) effective contraceptive methods. Menstrual irregularities, particularly were frequent and were the most common discontinuation.
are very
amenorrhoea, reasons for
DMPA had a slightly better continuation rate in spite caused more the fact that it menstrual of irregularities The less frequent than NET-EN. injections may be the reason for the better performance of DMPA. Injectable contraceptives Egyptian women who can disruptions.
are potentially acceptable by tolerate possible menstrual
Acknowledgements We thank WHO Special Programme of Research, Development and Research Training in Human Reproduction for supplying the drugs, subjects' random table and the follow-up booklets (Study No.: 82005).
References 1.
Injectable steroids as a method Karim M, Mahgoub S El. Medical Journal Shams contraception. Ain of 1970:21:543.
2.
The Mahgoub S El, Karim, M. injectable DMPA as a contraceptive. Scan 1972;51:25.
3.
Mahgoub S El, Karim M. The long-term use of injectable Contraception 1972;5:21. NET-EN as contraceptive.
4.
Nash H. 1975:12:377.
708
Depoprovera,
a
long-term use of Acta Obstet Gynecol
review.
DECEMBER
Contraception
1988 VOL. 38 NO. 6
CONTRACEPTION
5.
World Expanded Programme of Health Organization. Research, Development and Research Training in Human Reproduction. Task Force on Long-Acting Systemic Agents for the Regulation of Fertility. Multinational evaluation of two comparative clinical long-acting injectable contraceptive steroids: NET-EN and DMPA: 1. Use-effectiveness. Contraception 1978;15:513-533.
6.
World Expanded Programme of Health Organization. Research, Development and Research Training in Human Reproduction. Task Force on Long-Acting Systemic Agents for the Regulation of Fertility. Multinational comparative clinical evaluation of two long-acting injectable contraceptive steroids: NET-EN and DMPA: 2. Bleeding and side effects. Contraception patterns 1978;17:395-406.
7.
Fraser IS, Weisberg E. A comprehensive review of injectable contraception with special emphasis on DMPA. Med J Australia 198l;l(special suppl):l-19.
8.
SA. Shaaban MM, Salah M, Zarzo r A, Abdullah prospective study of Norplant w implants and TCu380 IUD in Assiut, Egypt. Stud Fam Plann 1983;14:163.
9,
Kesseru-Koos E, Larranaga-Leguia A, Scharff HJ. Fertility control with acting parenteral progestogen. Acta 1973;4:203.
10.
Soutchfield injectable 1971;3:21.
11.
Schwallie PC, Assenzo TR. Contraceptive use-efficacy study utilizing MPA administered as an intramuscular injection once days. Fertil Steril every 90 1973;24:331.
12.
Ali MM, Jalil MA. Further study on the effect of NETEN, an injectable contraceptive, on body functions. Bangladesh Med Res Council Bull 1978;4:63.
13.
Black HR, Leppert P, DeCherney A. blood pressure. Internat J Gynecol
14.
Dahlberq K. Some effects nursing infant and in the Gynecol Obstet 1982:20:43.
15.
Apelo RA, DelaCruz JR, Caucio-Lopez of injectable contraception in the Med Bull 1974;8:1.
DECEMBER
A Ag
Hurtado-Koos H, NET-EN a longEuropoea Fertil
FD, Long WN, Corey B, Tyler female contraceptive.
MPA as an W. Contraception
The effect of MPA on Obstet 1979;17:83.
of MPA: Observation in the long-term users. Internat J
1988 VOL. 38 NO. 6
F. Acceptability Philippines. IPPF
709
CONTRACEPTION
16.
World Organization. Special Health Programme of Research, Development and Research Training in Human Reproduction. Task Force on Long-Acting Systemic Agents for the Regulation of Fertility. Multinational comparative clinical trial of long-acting injectable contraceptives: NET-EN given in two dosage regimens and DMPA: A preliminary report. Contraception 1982;25:1.
17.
Castandeda lea1 A, Rios Castro B. Clinical study of MPA in Family Planning Programme. In: Contraceptive Progress in Latin America and Caribbean (Sanhueza H, Jamies R, eds). Proceedings of the IPPF/WHR 2nd Regional Medical Seminar, Medellin, Colombia, Nov. 25Parenthood (IPPF), p 26, 1975. New York, International 16, 1976.
18.
Banerjee SK, Baweja Raj, Bahtt RV, et al. Comparative evaluation of contraceptive efficacy of norethisterone cenanthate (200 mg) injectable contraceptive given 1984:30:561. every two or three monthly. Contraception
710
DECEMBER
1988 VOL. 38 NO. 6
ACCEPTABILITY
OF INJECTABLE
CONTRACEPTIVES
IN ASSIUT,
EGYPT
H.T. Salem*, M. Salah, M.Y. Aly, A.I. Thabet, M.M. Shaaban and M.F. Fathalla
Department
of Obstetrics and Gynaecology Assiut, Egypt
Abstract The present work was a randomized comparative study of two injectable progestogen-only contraceptives. The first (200 subjects) received 150 of depotgroup medroxyprogesterone acetate (Depoprovera) t:ery 8427 days and the second (200 subjects) received 200 mg of norethisterone enanthate (Noristerat) every 56+7 days. Acceptors of injectable contraceptives in Assiut, Egypt, were mainly women looking for fertility termination. Menstrual disruption was the main side effect among both treatment groups. Amenorrhoea was the commonest menstrual complaint and was the main reason for discontinuation in both groups. Only one pregnancy occurred during NET-EN use; two more pregnancies occurred, one in each of the two groups but there were indications that conception preceded the first injection. Menstrual irregularities were generally more frequent with DMPA users. However, DMPA had better rates one-year continuation than NET-EN (68.823.5 and 57.1r3.6 per 100 women, respectively).
*To whom correspondence
should be addressed.
Submitted for publication March 31, 1987 Accepted for publication September 15, 1988
DECEMBER
1988 VOL. 38 NO. 6
697
CONTRACEPTION
Introduction Injectable contraceptives have now been in use for over two decades in some 80 countries and by over 10 million women. In Egypt they have been used only on a limited scale and for research purposes (l-3). Injectable contraceptives have the advantages of being very effective methods and require administration every two or three months (l-7). The idea of long-acting contraceptives is welcomed by Egyptian women (8). This has prompted studying the use of injectable contraceptives in different parts of Egypt. In the present study we have conducted a randomized comparative field trial in the use of depot-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN) in Assiut, Egypt, to evaluate the performance of the two injectables in the community as regards side effects, continuation and terminations. The hypothesis is that the menstrual performance of the two preparations might differ in a way that influences continuation rates. Material
and Method
Four-hundred women were recruited from among those attending the El-Welledia Family Planning Center in Assiut, Based on a random table, 200 women started use of Egypt. Randomization table was DMPA and 200 started use of NET-EN. prepared by the WHO, Special Programme of Research, in Human Reproduction. Development and Research Training The women were allocated by picking a seated envelope which had a number that assigned her to one of the two methods. Before they were accepted into the study, all women underwent a physical examination and were given information about the method to be used and the possible side effects. The inclusion criteria were: - Age between 18 and 40 years. - Women with proven fertility and with frequent exposure to the risk of pregnancy. - Regular menstrual cycles. - Willingness to rely only upon this method. - Willingness and ability to return at the scheduled follow-up visits. The exclusion
criteria
were:
-
Breast-feeding. Present or past cardiovascular disease. Present or past liver disease. Known or suspected breast malignancy. Known or suspected genital malignancy or uterine fibroids. - Undiagnosed vaginal bleeding. - Suspected pregnancy.
698
DECEMBER
1988 VOL. 38 NO. 6
CONTRACEPTION
The regimen used for DMPA was 150 mg given by deep I.M. injection every three months and that for NET-EN was 200 mg for one year. At each scheduled I.M. every two months visit, spontaneous complaints were recorded together with the details of menstrual changes, blood pressure, weight and These were date of physical examination. recorded on WHO special records designed by Special Programme of Development and Research Training in Research, Human Reproduction. No list of complications was read to the users. Women who complained of heavy and/or prolonged bleeding were first examined to exclude possible gynaecological lesions and were evaluated for anaemia and given iron supplements accordingly. If bleeding persisted, the subject was referred for D&C biopsy and was excluded from the study. For women who had no menstruation for at least 8 weeks during the first 6 months of treatment, pregnancy was excluded by pelvic examination, pregnancy test and ultrasonography.
Results Table I gives the characteristics of the acceptors. The mean ages of DMPA and NET-EN users were 32.4 and 33.1, respectively, with women 35 years or more representing more than half of each group. The mean parity of DMPA users was 6.4, and 69.5% of the women had 5 or more previous deliveries. The mean parity of NET-EN users was 6.6, and 80.5% of the women had 5 or more previous deliveries. About 54.5% of DMPA users were from urban areas, while 45.5 were from rural areas. For NET-EN the percentages were equal. The outcome of last pregnancy was live-birth in 94% of DMPA users and 93% of NET-EN users. About two-thirds of acceptors of both methods had been currently using other methods of contraception prior to admission to the study. Oral contraceptives represented the most commonly used method (90%). Menstrual complaints among DMPA users are given in Table II and Figure 1. While 37.3% reported no menstrual problem 3 months after using DMPA, 27.1% of those who came to the la-month follow-up (107 women) had no complaints. Amenorrhoea was reported most frequently with its incidence increasing with time (from 30.8% after 3 months to 55.1% by the end of the year). The other menstrual complaints such as irregular bleeding, spotting, heavy bleeding and oligohypomenorrhoea and/or hypomenorrhoea generally tended to remain steady or diminish in those women who continued to use the method up until the end of the first year.
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CONTRACEPTION
Table I :
Religion
and socio-demographic
characteristics
of the acceptors
DMPA
NET-EN
No.
%
No.
%
153 47
76.5% 23.5?6
161 39
80.5% 19.5%
Urban* Rural
109 91
54.5% 45.5%
100 100
50.0% 50.0%
20 25 30 35
14 38 4G 102
7.0?$ 19.0% 23.0% 51.0%
5 35 55 105
2.5% 17.5% 27.5% 52.5%
:
- Religion
Moslems Christians
:
- Residence
- Age : -
24 29 34 39
- Mean age -+ S.D. - Parity : l-2 3-4 5-6 7-6 9 - Mean parity * By urban
+ S.D.
area
is meant
32.4 + 5.7 12 49 46 49 44
33.1 + 5.0 4 35 60 60 41
6.0% 24.5% 23.0% 24.596 22.0% 6.2 -+ 2.9
the governorate
capital
Table II : Incidence of menstrual complaints months after acceptance (?b)
6.6 + 2.3 and main cities.
among
DMPA
users
by
Months after
acceptance
(n=F21)
(n=9107)
(n=11207)
33 (30.8?&)
(27?%)
41 (33.9%)
50 (46.8%)
59 (55.1%)
13??$
17 (15.9?9
( 91&x,
( 5.i%)
( 3.:w1
3 ( 2.0%)
( A)
( 1.9%)
None Amenorrtoea Irregular
2.0% 17.5% 30.0% 30.0?6 20.5%
bleeding
Spotting Heavy bleeding Oligomenorrhoea hypomenorrhoea
700
and/or
2 3 (2.5%)
DECEMBER
1 ( 0.9%)
1988 VOL. 38 NO. 6
CONTRACEPTION
Irreg. bl. +.-spot. \,
_
_
_e+-
-
d
. .
---=--y.
H.bl.3 3
6
Duration
Figure 1:
-
9
_h12
(months)
Menstrual
problems
acceptors
during one year of use
reported by DMPA
None = No menstrual abnormalities Irreg. bl. = Irregular bleeding H. bl. = Heavy bleeding Am. = Amenorrhoea spot. = Spotting
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CONTRACEPTION
Table III:
Incidence of menstrual complaints months after acceptance (%)
among NET-EN users by
Months after --(n=l256) None
(n=143I)
(n=FIl)
84 66 64 (53.996) (50.436) (57.S)
acceptance (n=YOl)
(n=l”,4)
(464k)
(333k)
(302&J
(3&)
(421&b)
Amenorrhoea (18296%) (2&) Irregular bleeding
(27??&) (323k)
7 17 12 ( 6.396) (11.996) (18.1?6)
(l6tko) 2
Spotting
( 2.lS) Heavy bleeding
( Z.f?&) Oligomenorrhoea and/or hypomenorrhoea ( 5.796) ( 6.196) ( 1.876) ( l.OS) ( 0.096) ( 6.k)
Menstrual complaints among NET-EN users are shown in Table III and Figure 2. While 53.9% reported no menstrual problem 2 months after using NET-EN, 30.9% had no menstrual complaints at the end of the year. Amenorrhoea was reported most frequently with its incidence increasing with time (from 18.6 at 2 months to 42.5% by the end of the year). Irregular bleeding was reported next in frequency with its incidence increasing with time. Complaints of oligohypomenorrhoea and/or hypomenorrhoea also slightly increased with time. Only complaints of spotting and heavy bleeding diminished with time. Among DMPA users, headache was reported most frequently with its incidence slightly increasing with time (from 11.6% at 3 months to 15% at the end of the year). Next in frequency and with increasing incidence were abdominal distension and low backache. The incidence of the vague complaint of general weakness diminished with time, reaching 3.7% by the end of the year. Lower abdominal distension was reported by only 1.9% at the end of the year. Partial hair loss was reported by only 1.9% at 9 months and by 2.8% by the end of the year.
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% 70
60
50
40
30
20 Irreg.bl.&
-
- -?,
10
,
.X'
.
Duration
Figure 2:
P---___
.,.
(months)
Menstrual
problems
reported by NET-EN
acceptors
during one year of use.
None = No menstrual abnormalities Irreg. bl. = Irregular bleeding H. bl. = Heavy bleeding Am. = Amenorrhoea spot. = Spotting
DECEMBER
1988 VOL. 38 NO. 6
703
46
57
-
NET-EN
- DMPA
Decrease
28.0
la.1
30
17
- NET-EN
60.6
43.0
- DMPA
- No change
-
29.0
21.3
31
20
%
- DhlPA
No.
5-40
5-35
S-20
5-35
Range
Systolic
i6.a+a.a
13.7+7.3
lo.az5.4
13.2ta.3
Mean+S.D.
28.9 23.4
31 22
53.3 59.6
51 56
17.8 17.0
16
%
19
No.
Blood Pressure
S-20
5-20
5-20
S-30
Range
Diastolic
9.4 6.4
l-l.!
6
1-a
16.8
1-21
21.3
l-20
72.3
Rnnge
73.8
. 90
10
la 20
9.~~4.0
68
lO.dz5.1
79
9.024.9
No.
10.5L6.6
b1ean~S.D.
Keight
Classification of DMPA and NET-EN users at the end of the study according to net changes in blood pressure and weight
- NET-EN
- Increase
Table IV:
3.423.0
3.6z1.9
4.723.3
5.5+3.9 _
Mcnn+S.D.
CONTRACEPTION
Table V:
One-year cumulative termination and continuationrates per 100 acceptors,and events,firstsegment of use Rates DMPA
Pregnancy Bleeding Amenorrhoea Other medical Other personal Planning pregnancy Total termination Continuation Lost to follow-up Women-years of use
0.5+0-s 8.172.1 10.672.3 2.271.1 3.671.4 6.371.8 31.3T3.5 68.873.5 l?i6
Events NET-EN
1.0+0.7 12.572.4 13.072.5 5.971.7 4.471.5 6.171.8 42.973.6 57.173.6 13T50
* Faulty selection was most probably pregnancy in each treatment group.
DMPA
NET-EN
1* 14 19 4 6 11 55 107 145.7
2* 23 24 11 8 11 7s 34 139.6
the cause of one
reported was most users, headache NET-EN Among increasing with time (from frequently with its incidence The 3.2% at 3 months to 19.4% by the end of the year). distension abdominal low backache and incidences of by increased with time, reaching 5.3 and 3.2, respectively, The incidence of the vague complaint the end of the year. of general weakness diminished with time, reaching 5.3% by the end of the year. Table IV gives the changes in blood pressure and weight BY the end of the year, there among DMPA and NET-EN users. was a statistically significant decrease in the systolic and for both DMPA and NET-EN users. diastolic blood pressures The percentage of users who showed a decrease in systolic and diastolic blood pressures was higher among the NET-EN group than among the DMPA group (61% for the systolic and 60% for the diastolic in the NET-EN group versus 43 and 53 in the DMPA group). There was a statistically insignificant increase in the mean body weight of acceptors of both DMPA and NET-EN. About three-fourths of each group showed an increase in body weight. The reasons for terminations are shown by the lifeOne pregnancy was table rates and events in Table V. detected among DMPA users and two among NET-EN users. However, judging from the duration of pregnancy at the first one pregnancy in each group was due to faulty follow-up,
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CONTRACEPTION
This resulted from selection rather than method failure. the women giving false data about the date of their last The outcome of pregnancies was two males and menstruation. one female who were healthy with no apparent abnormalities. The two most important causes of discontinuation among both groups of contraceptive users were amenorrhoea and for 19 Amenorrhoea accounted bleeding problems. terminations among DMPA users with a net rate of 10.6 per 100 women at one year and for 24 terminations among NET-EN users with a net rate of 13.0 per 100 women at one year. Bleeding problems accounted for 14 terminations among DMPA users and 23 terminations among NET-EN users with net rates of 8.1 and 12.5 per 100 women, respectively. The one-year continuation rates were 68.8 and 57.1 per 100 women for the DMPA and NET-EN groups, respectively. Discussion injectable acceptors of study the In the present for fertility women looking were mostly contraceptives termination rather than for spacing: most of the subjects were relatively older (mean ages 32 and 33 years) and of high parity (mean parity 6.6 and 6.4) for DMPA and NET-EN, The age and parity of injectable acceptors respectively. are comparable to those of implant acceptors in the same locality (8). Menstrual disruptions were the main side effects among both treatment groups and generally were more common with DMPA than NET-EN users. Amenorrhoea was the most frequent menstrual complaint and was more frequent with DMPA, and its incidence increased with time. At the end of one year, 55% and 42.5% of DMPA and NET-EN acceptors, respectively, were amenorrhoeic. A WHO multicentre clinical trial (6) reported that by the end of one year use of DMPA, 35% of acceptors became amenorrhoeic and that the incidence of amenorrhoea increased with duration of use. With NET-EN users the incidence of amenorrhoea after one year of use was reported to be lo-25% (3,9), a much lower incidence than that found in the present study. Bleeding was also more common with DMPA than with NET-EN (31.5% and 27.5%, respectively) at the first follow-up visit. However, by the end of one year, there was a decrease in the incidence of bleeding among both treatment groups. Headache was the most common non-menstrual complaint and was more frequent among DMPA users. It was time related and its incidence increased with prolonged use. Other studies also showed that headache was reported as the most common non-menstrual complaint of women using injectable contraceptives (6,10,11).
706
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1988 VOL. 38 NO. 6
CONTRACEPTION
but With both treatment groups there was a slight, in the mean systolic and diastolic significant, decrease blood pressures which was more apparent with the NET-EN Most studies have reported insignificant changes acceptors. in women using in systolic and diastolic blood pressure either DMPA or NET-EN (6,7,12-14). After one year of use there was an insignificant in the mean body weight of acceptors of both increase groups. Weight gain was welcomed by most Egyptian women, especially in rural areas. A similar observation was reported in the Philippines (15). The one-year continuation rates for DMPA and NET-EN These were 68.8 and 57.1 per 100 women-years, respectively. rates are lower than the respective rates reported by the first WHO multicentre study (5) which were 71.2 and 75.6, but higher than those reported by the second WHO clinical trial (16), 48.6 and 50 per 100 women-years, respectively. The main cause of discontinuation was amenorrhoea (10.6 and 13 per 100 women for DMPA and NET-EN, respectively). Although amenorrhoea was more common among DMPA users, the discontinuation for amenorrhoea was higher for NET-EN users. The more convenient 3-monthly regimen of DMPA is a possible explanation. Culturally, especially in rural areas, amenorrhoea is regarded as a sign of ill health as menstruation is essential to get rid of "bad bloodS1 which causes headache, lethargy, abdominal distension and a sense of general ill health. Furthermore, amenorrhoea creates in some women a fear of pregnancy, infertility, menopause or onset of senility. Bleeding was the next common cause of discontinuation (8.1 and 12.5 per 100 women-years for DMPA and NET-EN, respectively). The discontinuation rate for DMPA is than bleeding irregularities for lower those reported by WHO (9.3 and 15.1 per 100 women-years) (5,16). The majority of the population in our locality are Moslems and these bleeding problems are poorly tolerated as they duties such as praying and will interfere with religious Ramadan fasting besides interfering with sexual activities. Three cases of pregnancy occurred during this study (one with DMPA and two with NET-EN). In fact, fault of selection was the cause of one pregnancy in each treatment group, as they received the first injection too late after menstruation. The pregnancy rate for DMPA in the present study is similar to other studies using the same dosage regimen With NET-EN, the pregnancy rate in this study is (5,6,17). similar to that reported by the WHO multicentre also
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CONTRACEPTION
clinical trial (16) using NET-EN in a regimen of 200 mg every 8 weeks throughout the study. Unacceptably higher pregnancy rates have been reported when NET-EN injection was given every 12 weeks after the first 4 injections (18).
Conclusions Injectable contraceptives (DMPA and NET-EN) effective contraceptive methods. Menstrual irregularities, particularly were frequent and were the most common discontinuation.
are very
amenorrhoea, reasons for
DMPA had a slightly better continuation rate in spite caused more the fact that it menstrual of irregularities The less frequent than NET-EN. injections may be the reason for the better performance of DMPA. Injectable contraceptives Egyptian women who can disruptions.
are potentially acceptable by tolerate possible menstrual
Acknowledgements We thank WHO Special Programme of Research, Development and Research Training in Human Reproduction for supplying the drugs, subjects' random table and the follow-up booklets (Study No.: 82005).
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Injectable steroids as a method Karim M, Mahgoub S El. Medical Journal Shams contraception. Ain of 1970:21:543.
2.
The Mahgoub S El, Karim, M. injectable DMPA as a contraceptive. Scan 1972;51:25.
3.
Mahgoub S El, Karim M. The long-term use of injectable Contraception 1972;5:21. NET-EN as contraceptive.
4.
Nash H. 1975:12:377.
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Depoprovera,
a
long-term use of Acta Obstet Gynecol
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World Expanded Programme of Health Organization. Research, Development and Research Training in Human Reproduction. Task Force on Long-Acting Systemic Agents for the Regulation of Fertility. Multinational evaluation of two comparative clinical long-acting injectable contraceptive steroids: NET-EN and DMPA: 1. Use-effectiveness. Contraception 1978;15:513-533.
6.
World Expanded Programme of Health Organization. Research, Development and Research Training in Human Reproduction. Task Force on Long-Acting Systemic Agents for the Regulation of Fertility. Multinational comparative clinical evaluation of two long-acting injectable contraceptive steroids: NET-EN and DMPA: 2. Bleeding and side effects. Contraception patterns 1978;17:395-406.
7.
Fraser IS, Weisberg E. A comprehensive review of injectable contraception with special emphasis on DMPA. Med J Australia 198l;l(special suppl):l-19.
8.
SA. Shaaban MM, Salah M, Zarzo r A, Abdullah prospective study of Norplant w implants and TCu380 IUD in Assiut, Egypt. Stud Fam Plann 1983;14:163.
9,
Kesseru-Koos E, Larranaga-Leguia A, Scharff HJ. Fertility control with acting parenteral progestogen. Acta 1973;4:203.
10.
Soutchfield injectable 1971;3:21.
11.
Schwallie PC, Assenzo TR. Contraceptive use-efficacy study utilizing MPA administered as an intramuscular injection once days. Fertil Steril every 90 1973;24:331.
12.
Ali MM, Jalil MA. Further study on the effect of NETEN, an injectable contraceptive, on body functions. Bangladesh Med Res Council Bull 1978;4:63.
13.
Black HR, Leppert P, DeCherney A. blood pressure. Internat J Gynecol
14.
Dahlberq K. Some effects nursing infant and in the Gynecol Obstet 1982:20:43.
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Apelo RA, DelaCruz JR, Caucio-Lopez of injectable contraception in the Med Bull 1974;8:1.
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Hurtado-Koos H, NET-EN a longEuropoea Fertil
FD, Long WN, Corey B, Tyler female contraceptive.
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The effect of MPA on Obstet 1979;17:83.
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World Organization. Special Health Programme of Research, Development and Research Training in Human Reproduction. Task Force on Long-Acting Systemic Agents for the Regulation of Fertility. Multinational comparative clinical trial of long-acting injectable contraceptives: NET-EN given in two dosage regimens and DMPA: A preliminary report. Contraception 1982;25:1.
17.
Castandeda lea1 A, Rios Castro B. Clinical study of MPA in Family Planning Programme. In: Contraceptive Progress in Latin America and Caribbean (Sanhueza H, Jamies R, eds). Proceedings of the IPPF/WHR 2nd Regional Medical Seminar, Medellin, Colombia, Nov. 25Parenthood (IPPF), p 26, 1975. New York, International 16, 1976.
18.
Banerjee SK, Baweja Raj, Bahtt RV, et al. Comparative evaluation of contraceptive efficacy of norethisterone cenanthate (200 mg) injectable contraceptive given 1984:30:561. every two or three monthly. Contraception
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