- Email: [email protected]
Norethisterone oenanthate as an injectable contraceptive: A study of patients discontinuing treatment
CONTRACEPTION
NORETHISTERONE OENANTHATE AS AN INJECTABLE A STUDY OF PATIENTS
CONTRACEPTIVE:
DISCONTINUING TREATFIEHT
O.F. Giwa-Osagie, J. Savage and J.R. Newton Department of Obstetrics and Gynaecology and World Health Organisation Collaborating Centre for Clinical Research on Human Reproduction, King's College Hospital, Denmark Hill, London, SE5 8RX, England
ABSTRACT Two hundred and ninety-five women were enrolled in a study of norethisterone oenanthate (NET-OEN) as an injectable contraceptive. One hundred and twenty-four patients whodiscontinuedthis contraceptive have been studied in detail. The main reasons for use-related closures of method were menstrual abnormality (22 patients), minor side-effects (23 patients), personal reasons (22 patients) with 18-month life-table net discontinuation rates of 14.7/100 women, 13.5/100 women, 14.2/100 women respectively and an overall discontinuation rate of 49.2/100 women. There were no accidental pregnancies. The probability of discontinuing treatment was not affected by age, parity, time of starting treatment or previous contraception. Sixty-nine per cent of all discontinuations occurred in the first four months of treatment. There were no serious complications.
Accepted
NOVEMBER
for Dublication
October
1978 VOL. 18 NO. 5
16, 1978
517
CONTRACEPTION
Introduction For over a decade, long-acting progestogens have been used for Depot-medroxyprogesterone acetate contraception in several countries. (DMPA) is the most widely used injectable contraceptive. Norethisterone oenanthate (NET-OEN), the heptanoic ester of norethisterone, may have certain advantages over DMPA. In a comparison of NET-OEN and DMPA given every 12 weeks,it was found that the accidental pregnancy rate for NET-OEN was significantly higher than that for DMPA but,that with NET-OEN, users had a lower incidence of amenorrhoea as well as fewer discontinuations for amenorrhoea (1,2). In the United Kingdom, DMPA has been approved by the Committee on Safety of Medicines (CSM) for short-term use only. Experience with injectable contraceptives is therefore limited Although it is important to know what happens to patients continuing contraceptive use, it is essential to know why patients discontinue treatment as this might aid the selection of contraceptive for patients. We have studied NET-OEN at King's College Hospital since 1975. A modified dose schedule has been used (4) and this report is about patients who discontinued treatment.
(
Patients and Methods Patients were recruited from the Family Planning Clinics, gynaecological and postnatal wards of King's College Hospital, between December 1975 and September 1977. Thev were all healthy, aqe 18 to 45 and with reqular menstrual cycles - the d?fference between-the-longest and shortest cycles in the preceding three months did not exceed 10 days. Patients who had recently been pregnant were required to have had regular cycles in the No patient had hormone treatment in three months before their pregnancy. A detailed history was obtained the four weeks before starting treatment. from each patient and a full medical and gynaecological examination was Informed consent was obtained. performed. NET-OEN was supplied by Schering A.G. Berlin in lml vials containing The vial containing the drug was 200mg of the drug in an oily solution. warmed in hot water and the drug was then given by intramuscular injection In menstruating patients, the first injection into the gluteal muscles. In postnatal was given during day one to five of a menstrual period. patients and patients who had had a termination of pregnancy, the first The second, third and injection was given before discharge from hospital fourth injection were given at eight-week intervals so that each patient received four injections during the first six months of treatment. Subsequent injections were given at 12-week intervals. At each scheduled visit, body weight, blood pressure and menstrual Any complaints were noted and appropriate advice history were recorded. or treatment given. All injections were given within seven days of the scheduled date. For all patients who discontinued treatment,the reason for discontinuation and the alternative method of contraception chosen was noted. The absence of periods for 90 days or more was recorded as amenorrhoea. The absence of regular periods as well as intermittent vaginal bleeding requiring no sanitary protection were recorded as "irregular bleeding".
518
NOVEMBER
1978 VOL. 18 NO. 5
CONTRACEPTION
Continuous vaginal bleeding for more than 10 days was recorded as "prolonged bleeding". Patients were recorded as lost to follow-up (LFU) if they were more than 7 days overdue for a scheduled visit and if no information was If a patient then returned obtained by telephone, mail or home visit. to the clinic more than 7 days after a scheduled visit,she was offered alternative contraceptive advice. Life-table analysis (5,6) was applied to the gata giving 'gross' and 'net' event rates. Student's t test and the X test were used to compare groups of patients.
Results During the period of study, 124 patients discontinued treatment. Tables I and II show the life-table analysis for use related closures of method. The use related discontinuation rate was 39.1/100 women at 12 months and 49.2/100 women at 18 months. Of the closures at 18 months, 22 patients had discontinued treatment because of menstrual abnormality, 22 patients for personal reasons, 23 patients for minor side-effects, with net discontinuation rates of 14.7, 14.2 and 13.5/100 women,respectively. The discontinuation rate for amenorrhoea was 1.4/100 women. Of the patients who discontinued for personal reasons, 13 patients no longer required contraception or had been sterilised, while among those who discontinued for minor sideeffects were 10 patients who stopped treatment because they had added more than 3kg weight, three patients who had various aches and pains and two patients who felt bloated. The two closures for major side-effects were because of raised blood pressure, the diastolic pressure being 105mm Hg or more during treatment. In all,52 patients here recorded as LFU, 30 of them because they failed to attend for injection within seven days of the scneduled date, and 22 patients (7.4.) kho refused to attend and e-ither went to their own family practitioner fcr contraception, left the District:, no longer required contraception or had left an incorrect address alid so could not be traced. Table: III compares the age and parity of (a) those continuing treatment with (b) :hcse who discontinued treatment. StL'dent's t test showed no significant diCference in age (p < 2.3 > 0.i) or peril-y (p < 0.5 > 0.1). Table IV compares :he numbers of patients starting treatment during a menstrual period or following a pregnancy among (a),th,?se continuing treatment and (b) those discontinuing treatment. XL t?st showed that the time of starting treatment did not affect the probabi;ity of discontinuing treatment (p > 0.1 c 0.5j. Tab12 \; lists the previous contraceptive used by those continuing treatment and those discontinuing treatment. Previous use of oral contraceptive or the intrauterine device die not affect the probability of discontinuation (X2 test, p > 0.5). Table VI gives the percentage of patients discontinuing treatment by ordinal month of completed use. Sixty-nine per cent of all discontinuations occurred during the first four ordinal months of use.
NO-v'EMBEK
1978 VOL.
18 NO.5
CONTRACEPTION
;;‘-
hh
C-XI vv--
r.
7
0mwul . --(CO +I
.
.
+I
+I
.
.
dddl.0 . -
7
m
. +I .
0
07
-.-.a-
cur--rv--v
0mr.m .
.
.
.
Yr-70
+I
+I
-=f’dmm . .
fl
+I .
.
---wcnlC.-d-UIO~U) . . .
.
7cc)LDO
07-O +I *wP)m .
fl
+I .
.
fl .
ONTO
520
NOVEMBER
1978 VOL. 18 NO. 5
CONTRACEPTION
--c\l-
cur.rr-v-v
*m*w . . __
r;d
t,
+I
+I
cnmww . .
+I
.
.
7mcuo
E;-.
-cur.r-r-v-v
Ktmcuw . . C---NO fl
.
+I fi
mcnww . . cc.
.
fi .
ul
. 0
he---__
--corn--
-v
W-LOW
d fl
,‘ ,’ i-i fl
w)cocnw . . 0 l-4
NOVEMBER
197X VOL. 18 NO. 5
d:
d +i . 0
521
CONTRACEPTION
Table III:
a)
b)
Patients continuing NET-OEN Age (years) mean f S.D.
:
Parity
:
b)
mean f S.D.
26.6 2 5.9 1.97 + 1.46
Patients discontinuing NET-OEN Age (years) mean + S.D.
:
Parity
:
Table IV:
a)
Age and parity, mean * 1 S.D., of (a) those continuing treatment and (b) those who discontinued treatment.
mean ? S.D.
27.1 _+ 6.0 2.19 + 2.39
Time of starting treatment among (a) those continuing treatment and (b) those who discontinued treatment.
Patients continuing NET-OEN:
(n = 171)
Started following pregnancy
:
53
Started during menstruation
:
118
~Patients discontinuing NET-OEPI: (n = 124) Started following pregnancy
:
32
Started during menstruation
:
92
NOVEMBEK
1978 VOL. IX NO. 5
CONTRACEPTION
Previous contraceptive used by study patients,
Table V:
Patients continuing NET-OEN
Patients discontinuing NET-OEN
Oral contraceptive
:
69
58
Intrauterine device
:
53
47
Barrier method
:
29
7
Coitus interruptus
:
5
1
Ho contraception
:
15
11
171
124
TOTAL
Percentage discontinuing treatment by ordinal month of completed use.
Table VI:
Ordinal Months
2
Percentage discontinuing
37.9
3-4
31.5
5-6
5.6
7-8
10.6
9 - 10
3.2
11 - 12
5.6
> 12
5.6
100
NOVEMBER
1978 VOL. 18 NO. 5
52.3
CONTRACEPTION
Discussion Using a modified injection schedule for NET-OEFI there were no accidental pregnancies in our study. A multinational study of NET-OEN (1,Z) had reported a pregnancy rate of 3.6/100 woman years in patients given NET-OEN every 12 weeks. Seventy-five per cent of the accidental pregnancies in that study occurred during the first three months of medication. A study of patients given only one injection of NET-OEN (7) had found that two out of eight patients ovulated around day 55 while five out of eight had ovulated by day 80. The improved contraceptive efficacy of NET-OEN given 8 weekly is probably due to a higher incidence of anovulation coupled with the recognised effects of the progestogen on cervical mucus. A higher incidence of anovulation can be expected to reduce the chance of pregnancy early in treatment. Serial hormone profiles during the first six months of treatment in our patients indicate that ovulation does not occur when the drug is given every eight weeks (2). Although we use an injection schedule that is more likely to produce anovulation, the discontinuation rate for amenorrhoea was similar to that reported for NET-DEN and less than the rates reported for DMPA users in the multinational study (2). Prolonged bleeding and irregular bleeding were the main forms of menstrual abnormality resulting in discontinuation. In our study, 68 per cent of all discontinuations for menstrual abnormality occurred in the first four months of NET-OEN use. If most discontinuations for menstrual abnormality occur early in treatment, the incidence of discontinuation later on can be expected to decrease. Other investigators (9) have reported an increase in regular menstruation and a decrease in the incidence of amenorrhoea with prolonged use of NET-OEII. Overall, 69 per cent of all discontinuations occurred in the first four ordinal months of treatment, It is clear from this that the most troublesome time for the patient is early in treatment and that if she tolerates the drug then, there is a high probability of her continuing treatment for more than one year. We were interested to find that the previous contraceptive used by the patient did not affect the probability of discontinuing treatment. In particular, patients who had previously taken oral contraceptives and were therefore used to the light regular periods characteristic of such contraception were not more likely to discontinue treatment when compared with patients who had previously used an intrauterine device. Similarly, the time of starting treatment did not seem to affect the probability of discontinuation - those patients who started treatment during a normal period were not more likely to discontinue treatment than those who started treatment immediately following abortion or confinement. The high number of patients recorded as LFU, 52 patients in 20 months, was mainly due to strict adherence to an injection schedule which required all injections to be given withinseven days of the scheduled date. Observations on MIPA, which produces a high incidence of anovulation and amenorrhoea, has led to concern about the return to fertility in
524
NOVEMBER
1978 VOL. 18 NO. 5
CONTRACEPTION
patients who have been on injectable contraceptives. Studies on NETOEN suggest the effect of the drug is reversed within six months Our own unpublished observations on of discontinuation (9,lO). patients who stopped NET-OEN contraception or who missed an injection suggest the same. The very low incidence of major side-effects was encouraging. Recent studies showed that blood clotting factors and glucose tolerance were not adversely affected by NET-OEM (11) and that the blood pressure is not adversely affected by NET-OEN (1). The Royal College of General Practitioners'study (12) further highlighted some dangers DMPA has been approved for shortof combined oral contraception. term contraceptive use by the Committee on Safety of Medicines. We feel that NET-OEW should be available to : any woman who requires highly effective contraception and who is prepared to tolerate irregular menstruation; women in whom oral contraception is contraindica ted because of the risk of thromboembolism; any woman who is waiting for hospital admission for sterilisation or who is waiting for her husband's vasectomy to be declared effective.
Acknowledgements We wish to thank Dr,P. Bye of Schering Pharmaceuticals for the supply of NET-OEN and for financial support; the Doctors and staff of the King's Family Planning Clinics for their help; Mrs.Back for typing this paper.
NOVEMBER
1978 VOL. 18 NO. 5
52.5
CONTRACEPTION
REFERENCES 1.
Benagiano, G.: In: Requlation Ed., Diczfalusy, E. Scriptor,
2.
Benagiano, G., Goldzieher, J.W. and Gray, R. Multinational Comparative Clinical Evaluation of Two LongActing Injectable Contraceptive Steroids: Norethisterone Oenanthate and Medroxyproqesterone Acetate. Contraception 5:513 (1977)
3.
Wilson, E. Domiciliary
4.
Giwa-Osagie, O.F., Savage, J. and Newton, J.R. Norethisterone Oenanthate as an Injectable Contraceptive: Use of a Modified Dose Schedule. Brit. Med. J. 1:1660 (1978)
5.
Recommended Procedures Tietze, C. and Lewit, S.: Statistical Evaluation of Intra-Uterine COntraCeptiOll. Studies in Family Planninq 4:35 (1973)
6.
Potter, R.G.: In Family Planning in Taiwan: An Experiment in Social Chanqe. Ed., Freedman,R. and Takeshita, J.Y. Princeton Eniversity Press, New Jersey (1969), 458
7.
Weiner, E. and Johansson, E.: The Influence of Norethisterone Oenanthate on Ovarian Function. Acta Endocrinologica (Kbh) 83:386 (1976)
8.
Giwa-Csagie, Preparation
9.
Kesserd-Koos, E., Hurtado-Koo, H., Larranaqa-Lequia, A., Fertility Control with Norethindrone and Scharff, H.J.: A Lonq-acting Parenteral Proqestoqen. Acta Enanthate. Europaea Fertilitatis 4:203 (1973)
of Human Fertility. Copenhagen (1977), 331
Use of Long-acting Depot Progestoqen in Family Planning. Brit. Med. J. 2:1435 (1976)
F., Newton, (1978)
J. and Collins,
W.P.:
for the
In
10.
Chinnatamby, S.: A Comparison of the Lonq-actinq Contraceptive Aqents Norethisterone Oenanthate and Aust. NZ J. Obstet. Gynaecol. Medroxyprogesterone Acetate. 11:233 (1971)
11.
Howard, G., Myatt, I,., and Elder, M.G.: The Lffects of Intramuscular Norethisterone Oenanthate Used as a Contraceptive on Intravenous Glucose Tolerance and on Blood Coaqulation Factors VII and X. Brit. J. Obstet. Gynaecol. 843618 (1977)
12.
Beral, V. Kav, C.R.: Mortality Among Oral Contraceptive Users. Royal College of General Practitioners' 2:727 (1977) The Lancet Oral Contraceptive Study.
526
NOVEMBER
1978 VOL. 18 NO. 5
NORETHISTERONE OENANTHATE AS AN INJECTABLE A STUDY OF PATIENTS
CONTRACEPTIVE:
DISCONTINUING TREATFIEHT
O.F. Giwa-Osagie, J. Savage and J.R. Newton Department of Obstetrics and Gynaecology and World Health Organisation Collaborating Centre for Clinical Research on Human Reproduction, King's College Hospital, Denmark Hill, London, SE5 8RX, England
ABSTRACT Two hundred and ninety-five women were enrolled in a study of norethisterone oenanthate (NET-OEN) as an injectable contraceptive. One hundred and twenty-four patients whodiscontinuedthis contraceptive have been studied in detail. The main reasons for use-related closures of method were menstrual abnormality (22 patients), minor side-effects (23 patients), personal reasons (22 patients) with 18-month life-table net discontinuation rates of 14.7/100 women, 13.5/100 women, 14.2/100 women respectively and an overall discontinuation rate of 49.2/100 women. There were no accidental pregnancies. The probability of discontinuing treatment was not affected by age, parity, time of starting treatment or previous contraception. Sixty-nine per cent of all discontinuations occurred in the first four months of treatment. There were no serious complications.
Accepted
NOVEMBER
for Dublication
October
1978 VOL. 18 NO. 5
16, 1978
517
CONTRACEPTION
Introduction For over a decade, long-acting progestogens have been used for Depot-medroxyprogesterone acetate contraception in several countries. (DMPA) is the most widely used injectable contraceptive. Norethisterone oenanthate (NET-OEN), the heptanoic ester of norethisterone, may have certain advantages over DMPA. In a comparison of NET-OEN and DMPA given every 12 weeks,it was found that the accidental pregnancy rate for NET-OEN was significantly higher than that for DMPA but,that with NET-OEN, users had a lower incidence of amenorrhoea as well as fewer discontinuations for amenorrhoea (1,2). In the United Kingdom, DMPA has been approved by the Committee on Safety of Medicines (CSM) for short-term use only. Experience with injectable contraceptives is therefore limited Although it is important to know what happens to patients continuing contraceptive use, it is essential to know why patients discontinue treatment as this might aid the selection of contraceptive for patients. We have studied NET-OEN at King's College Hospital since 1975. A modified dose schedule has been used (4) and this report is about patients who discontinued treatment.
(
Patients and Methods Patients were recruited from the Family Planning Clinics, gynaecological and postnatal wards of King's College Hospital, between December 1975 and September 1977. Thev were all healthy, aqe 18 to 45 and with reqular menstrual cycles - the d?fference between-the-longest and shortest cycles in the preceding three months did not exceed 10 days. Patients who had recently been pregnant were required to have had regular cycles in the No patient had hormone treatment in three months before their pregnancy. A detailed history was obtained the four weeks before starting treatment. from each patient and a full medical and gynaecological examination was Informed consent was obtained. performed. NET-OEN was supplied by Schering A.G. Berlin in lml vials containing The vial containing the drug was 200mg of the drug in an oily solution. warmed in hot water and the drug was then given by intramuscular injection In menstruating patients, the first injection into the gluteal muscles. In postnatal was given during day one to five of a menstrual period. patients and patients who had had a termination of pregnancy, the first The second, third and injection was given before discharge from hospital fourth injection were given at eight-week intervals so that each patient received four injections during the first six months of treatment. Subsequent injections were given at 12-week intervals. At each scheduled visit, body weight, blood pressure and menstrual Any complaints were noted and appropriate advice history were recorded. or treatment given. All injections were given within seven days of the scheduled date. For all patients who discontinued treatment,the reason for discontinuation and the alternative method of contraception chosen was noted. The absence of periods for 90 days or more was recorded as amenorrhoea. The absence of regular periods as well as intermittent vaginal bleeding requiring no sanitary protection were recorded as "irregular bleeding".
518
NOVEMBER
1978 VOL. 18 NO. 5
CONTRACEPTION
Continuous vaginal bleeding for more than 10 days was recorded as "prolonged bleeding". Patients were recorded as lost to follow-up (LFU) if they were more than 7 days overdue for a scheduled visit and if no information was If a patient then returned obtained by telephone, mail or home visit. to the clinic more than 7 days after a scheduled visit,she was offered alternative contraceptive advice. Life-table analysis (5,6) was applied to the gata giving 'gross' and 'net' event rates. Student's t test and the X test were used to compare groups of patients.
Results During the period of study, 124 patients discontinued treatment. Tables I and II show the life-table analysis for use related closures of method. The use related discontinuation rate was 39.1/100 women at 12 months and 49.2/100 women at 18 months. Of the closures at 18 months, 22 patients had discontinued treatment because of menstrual abnormality, 22 patients for personal reasons, 23 patients for minor side-effects, with net discontinuation rates of 14.7, 14.2 and 13.5/100 women,respectively. The discontinuation rate for amenorrhoea was 1.4/100 women. Of the patients who discontinued for personal reasons, 13 patients no longer required contraception or had been sterilised, while among those who discontinued for minor sideeffects were 10 patients who stopped treatment because they had added more than 3kg weight, three patients who had various aches and pains and two patients who felt bloated. The two closures for major side-effects were because of raised blood pressure, the diastolic pressure being 105mm Hg or more during treatment. In all,52 patients here recorded as LFU, 30 of them because they failed to attend for injection within seven days of the scneduled date, and 22 patients (7.4.) kho refused to attend and e-ither went to their own family practitioner fcr contraception, left the District:, no longer required contraception or had left an incorrect address alid so could not be traced. Table: III compares the age and parity of (a) those continuing treatment with (b) :hcse who discontinued treatment. StL'dent's t test showed no significant diCference in age (p < 2.3 > 0.i) or peril-y (p < 0.5 > 0.1). Table IV compares :he numbers of patients starting treatment during a menstrual period or following a pregnancy among (a),th,?se continuing treatment and (b) those discontinuing treatment. XL t?st showed that the time of starting treatment did not affect the probabi;ity of discontinuing treatment (p > 0.1 c 0.5j. Tab12 \; lists the previous contraceptive used by those continuing treatment and those discontinuing treatment. Previous use of oral contraceptive or the intrauterine device die not affect the probability of discontinuation (X2 test, p > 0.5). Table VI gives the percentage of patients discontinuing treatment by ordinal month of completed use. Sixty-nine per cent of all discontinuations occurred during the first four ordinal months of use.
NO-v'EMBEK
1978 VOL.
18 NO.5
CONTRACEPTION
;;‘-
hh
C-XI vv--
r.
7
0mwul . --(CO +I
.
.
+I
+I
.
.
dddl.0 . -
7
m
. +I .
0
07
-.-.a-
cur--rv--v
0mr.m .
.
.
.
Yr-70
+I
+I
-=f’dmm . .
fl
+I .
.
---wcnlC.-d-UIO~U) . . .
.
7cc)LDO
07-O +I *wP)m .
fl
+I .
.
fl .
ONTO
520
NOVEMBER
1978 VOL. 18 NO. 5
CONTRACEPTION
--c\l-
cur.rr-v-v
*m*w . . __
r;d
t,
+I
+I
cnmww . .
+I
.
.
7mcuo
E;-.
-cur.r-r-v-v
Ktmcuw . . C---NO fl
.
+I fi
mcnww . . cc.
.
fi .
ul
. 0
he---__
--corn--
-v
W-LOW
d fl
,‘ ,’ i-i fl
w)cocnw . . 0 l-4
NOVEMBER
197X VOL. 18 NO. 5
d:
d +i . 0
521
CONTRACEPTION
Table III:
a)
b)
Patients continuing NET-OEN Age (years) mean f S.D.
:
Parity
:
b)
mean f S.D.
26.6 2 5.9 1.97 + 1.46
Patients discontinuing NET-OEN Age (years) mean + S.D.
:
Parity
:
Table IV:
a)
Age and parity, mean * 1 S.D., of (a) those continuing treatment and (b) those who discontinued treatment.
mean ? S.D.
27.1 _+ 6.0 2.19 + 2.39
Time of starting treatment among (a) those continuing treatment and (b) those who discontinued treatment.
Patients continuing NET-OEN:
(n = 171)
Started following pregnancy
:
53
Started during menstruation
:
118
~Patients discontinuing NET-OEPI: (n = 124) Started following pregnancy
:
32
Started during menstruation
:
92
NOVEMBEK
1978 VOL. IX NO. 5
CONTRACEPTION
Previous contraceptive used by study patients,
Table V:
Patients continuing NET-OEN
Patients discontinuing NET-OEN
Oral contraceptive
:
69
58
Intrauterine device
:
53
47
Barrier method
:
29
7
Coitus interruptus
:
5
1
Ho contraception
:
15
11
171
124
TOTAL
Percentage discontinuing treatment by ordinal month of completed use.
Table VI:
Ordinal Months
2
Percentage discontinuing
37.9
3-4
31.5
5-6
5.6
7-8
10.6
9 - 10
3.2
11 - 12
5.6
> 12
5.6
100
NOVEMBER
1978 VOL. 18 NO. 5
52.3
CONTRACEPTION
Discussion Using a modified injection schedule for NET-OEFI there were no accidental pregnancies in our study. A multinational study of NET-OEN (1,Z) had reported a pregnancy rate of 3.6/100 woman years in patients given NET-OEN every 12 weeks. Seventy-five per cent of the accidental pregnancies in that study occurred during the first three months of medication. A study of patients given only one injection of NET-OEN (7) had found that two out of eight patients ovulated around day 55 while five out of eight had ovulated by day 80. The improved contraceptive efficacy of NET-OEN given 8 weekly is probably due to a higher incidence of anovulation coupled with the recognised effects of the progestogen on cervical mucus. A higher incidence of anovulation can be expected to reduce the chance of pregnancy early in treatment. Serial hormone profiles during the first six months of treatment in our patients indicate that ovulation does not occur when the drug is given every eight weeks (2). Although we use an injection schedule that is more likely to produce anovulation, the discontinuation rate for amenorrhoea was similar to that reported for NET-DEN and less than the rates reported for DMPA users in the multinational study (2). Prolonged bleeding and irregular bleeding were the main forms of menstrual abnormality resulting in discontinuation. In our study, 68 per cent of all discontinuations for menstrual abnormality occurred in the first four months of NET-OEN use. If most discontinuations for menstrual abnormality occur early in treatment, the incidence of discontinuation later on can be expected to decrease. Other investigators (9) have reported an increase in regular menstruation and a decrease in the incidence of amenorrhoea with prolonged use of NET-OEII. Overall, 69 per cent of all discontinuations occurred in the first four ordinal months of treatment, It is clear from this that the most troublesome time for the patient is early in treatment and that if she tolerates the drug then, there is a high probability of her continuing treatment for more than one year. We were interested to find that the previous contraceptive used by the patient did not affect the probability of discontinuing treatment. In particular, patients who had previously taken oral contraceptives and were therefore used to the light regular periods characteristic of such contraception were not more likely to discontinue treatment when compared with patients who had previously used an intrauterine device. Similarly, the time of starting treatment did not seem to affect the probability of discontinuation - those patients who started treatment during a normal period were not more likely to discontinue treatment than those who started treatment immediately following abortion or confinement. The high number of patients recorded as LFU, 52 patients in 20 months, was mainly due to strict adherence to an injection schedule which required all injections to be given withinseven days of the scheduled date. Observations on MIPA, which produces a high incidence of anovulation and amenorrhoea, has led to concern about the return to fertility in
524
NOVEMBER
1978 VOL. 18 NO. 5
CONTRACEPTION
patients who have been on injectable contraceptives. Studies on NETOEN suggest the effect of the drug is reversed within six months Our own unpublished observations on of discontinuation (9,lO). patients who stopped NET-OEN contraception or who missed an injection suggest the same. The very low incidence of major side-effects was encouraging. Recent studies showed that blood clotting factors and glucose tolerance were not adversely affected by NET-OEM (11) and that the blood pressure is not adversely affected by NET-OEN (1). The Royal College of General Practitioners'study (12) further highlighted some dangers DMPA has been approved for shortof combined oral contraception. term contraceptive use by the Committee on Safety of Medicines. We feel that NET-OEW should be available to : any woman who requires highly effective contraception and who is prepared to tolerate irregular menstruation; women in whom oral contraception is contraindica ted because of the risk of thromboembolism; any woman who is waiting for hospital admission for sterilisation or who is waiting for her husband's vasectomy to be declared effective.
Acknowledgements We wish to thank Dr,P. Bye of Schering Pharmaceuticals for the supply of NET-OEN and for financial support; the Doctors and staff of the King's Family Planning Clinics for their help; Mrs.Back for typing this paper.
NOVEMBER
1978 VOL. 18 NO. 5
52.5
CONTRACEPTION
REFERENCES 1.
Benagiano, G.: In: Requlation Ed., Diczfalusy, E. Scriptor,
2.
Benagiano, G., Goldzieher, J.W. and Gray, R. Multinational Comparative Clinical Evaluation of Two LongActing Injectable Contraceptive Steroids: Norethisterone Oenanthate and Medroxyproqesterone Acetate. Contraception 5:513 (1977)
3.
Wilson, E. Domiciliary
4.
Giwa-Osagie, O.F., Savage, J. and Newton, J.R. Norethisterone Oenanthate as an Injectable Contraceptive: Use of a Modified Dose Schedule. Brit. Med. J. 1:1660 (1978)
5.
Recommended Procedures Tietze, C. and Lewit, S.: Statistical Evaluation of Intra-Uterine COntraCeptiOll. Studies in Family Planninq 4:35 (1973)
6.
Potter, R.G.: In Family Planning in Taiwan: An Experiment in Social Chanqe. Ed., Freedman,R. and Takeshita, J.Y. Princeton Eniversity Press, New Jersey (1969), 458
7.
Weiner, E. and Johansson, E.: The Influence of Norethisterone Oenanthate on Ovarian Function. Acta Endocrinologica (Kbh) 83:386 (1976)
8.
Giwa-Csagie, Preparation
9.
Kesserd-Koos, E., Hurtado-Koo, H., Larranaqa-Lequia, A., Fertility Control with Norethindrone and Scharff, H.J.: A Lonq-acting Parenteral Proqestoqen. Acta Enanthate. Europaea Fertilitatis 4:203 (1973)
of Human Fertility. Copenhagen (1977), 331
Use of Long-acting Depot Progestoqen in Family Planning. Brit. Med. J. 2:1435 (1976)
F., Newton, (1978)
J. and Collins,
W.P.:
for the
In
10.
Chinnatamby, S.: A Comparison of the Lonq-actinq Contraceptive Aqents Norethisterone Oenanthate and Aust. NZ J. Obstet. Gynaecol. Medroxyprogesterone Acetate. 11:233 (1971)
11.
Howard, G., Myatt, I,., and Elder, M.G.: The Lffects of Intramuscular Norethisterone Oenanthate Used as a Contraceptive on Intravenous Glucose Tolerance and on Blood Coaqulation Factors VII and X. Brit. J. Obstet. Gynaecol. 843618 (1977)
12.
Beral, V. Kav, C.R.: Mortality Among Oral Contraceptive Users. Royal College of General Practitioners' 2:727 (1977) The Lancet Oral Contraceptive Study.
526
NOVEMBER
1978 VOL. 18 NO. 5