CONTRACEPTION
A Comparative Study of a Progestin-Only Oral Contraceptive versus Non-Hormonal Methods in Lactating Womenin Buenos Aires, Argentina
Angel V. Moggia,lM.D.‘, Gena S. Harris B.A.zi Thomas R. Dunson, M.S.‘:, Ruben Diaz, M.D. , Maria Su?ana Moggia, M.D. , Miguel A. Ferrer, M.D. , and Susan L. McMullen, M.A.
I9 de Julio 39, Bernal 1876, Buenos Aires, Argentina Research Triangle Park, NC 27709 USA 2Family Health International,
ABSTRACT A non-randomized comparative clinical trial of the progestin-only oral contraceptive (POC), Ovrette (75 mcg norgestrel) (Wyeth), versus non-hormonal methods was conducted at two clinics in Buenos Aires, Argentina. The trial was designed to assess the breastfeeding patterns of women choosing progestin-only oral contraception and non-hormonal methods of contraception, and to study the relationship between lactation and the clinical performance of a POC. Five-hundred women were allocated to either the progestin-only pill group (n = 250) or to the non-hormonal group (n = 250) and were followed up monthly for six months after admission. Measurements in mean infant weight, mean infant length, and mean head circumference were similar throughout the follow-up period. Non-hormonal users reported significantly more self-perceived decreases in milk production at the 5th and 6th month follow-up intervals. Acceptance and continued use of the pill were excellent, with only one womandiscontinuing because of a pregnancy The principal side effect which was attributed to user failure. reported by women in both groups was intermenstrual bleeding. *To whomrequests
for reprints
should be sent.
Submitted for publication January 31, 1991 Accepted for publication May 1, 1991
JULY 1991 VOL. 44 NO. 1
31
CONTRACEPTION INTRODUCTION During the postpartum period, prevention of pregnancy is important because birth spacings of two years or more results in significantly better infant and maternal health (l), because of the adverse effect pregnancy has on lactation (2), and because of the desire/need for limitation of family size. The immediate postpartum period is assumed to be a time when many women are receptive to family planning information and services. There is some concern about which contraceptive methods are most appropriate in the postpartum period, particularly for lactating women. In many countries, lactation is the infant’s only source of nutrition Some women, including those who are and protection against infection. breastfeeding their infants, prefer oral contraceptives. Yet there is concern about use of combined oral contraceptives during lactation because many studies have shown that lactation may be impaired by combined estrogen-progestin oral contraceptives (perhaps even those with relatively low doses of estrogen) (3-6). While the establishment of lactation may not be affected by these hormones, milk production, once established, frequently declines and lactation may cease On the other hand, previous research indicates that the prematurely. use of progestin-only oral contraceptives (POCs) during lactation does not appear to have adverse effects on lactation or infant growth and may even enhance lactation (5,7,8) . This study was designed to assess the breastfeeding patterns of women choosing progestin-only oral contraception and non-hormonal methods of contraception, and to study the relationship between lactation and the clinical performance of a POC. Two of the primary over time objectives in this study were to compare: (a) the difference in the weight of breastfed infants, and (b) the duration of and the unsupplemented breast feeding (i. e . , time to supplementation) duration of all breastfeeding (i.e., supplemented and unsupplemented breastfeeding) between women who used the progestin-only pill and women who did not use hormonal methods. As a third objective, the progestin-only group was evaluated for the acceptance and continued use of the pill. Also, the side effects experienced by women while taking the progestin-only pill were assessed and compared to those side effects experienced by women using non-hormonal methods. SUBJECTSAND METHODS Study Design From October 1985 to June 1987, women were admitted to two clinics in Buenos Aires, Argentina, the Jose Penna Hospital and the Policlinico Bernal. Two-hundred-fifty women were allocated to the progestin-only oral contraceptive group and 250 women were allocated to the non-hormonal contraceptive group. Women were asked to choose contraception and an array
32
between low-dose progestin-only of non-hormonal contraception.
oral Choice
of
JULY 1991 VOL. 44 NO. 1
CONTRACEPTION contraceptionwas not randomized. Women who elected non-hormonal methods were asked to give their reasons for not accepting progestin-onlypills: this was used as a measure of acceptability(or lack thereof) of POCs. Enrollmentin the study and initiationof pill use began within one week after delivery. Early initiationof pill use was chosen for two reasons. Early initiationmay be desirablein some settingswhere delivery is the only time a woman is in contact with the health care system. Therefore,it is importantto determinewhether such early initiationaffects the establishmentof lactation. Secondly,if no adverse effects of early initiationwere found in the study, then it would be unlikelythat later initiationwould be detrimental (7). For women who chose to use the IUD, the devices were insertedwithin one week postpartumand usually towards the end of that week, thus closely parallelingearly pill initiation. The other coitus-related methods chosen were all initiatedwhenever coitus was resumed. All of the women were breastfeedingat the time of admission. Women were asked to breastfeedevery three hours with an intervalbetween the last one at night and the first one of the followingday. The women in this study were given no additionalcounselingor support in breastfeeding,other than that which was normally given to breastfeedingmothers. Infantswere weighed and measured at admissionand at each of six monthly follow-upvisits. Breastfeedingepisodes and bleeding patterns reportedby the women at their f.ollow-up visits were based on retrospectiverecall. Bleeding pattern reports were based on the subjectiveinterpretationof each woman, and not from bleeding records or other objectivemeasures. Oral ContraceptiveEvaluated The progestin-onlypill supplied in this study, Ovrette (Wyeth, Philadelphia,PA), is composedof 75 mcg norgestreland is provided in 28-day packages. All pills contain active ingredientsand must be taken daily for proper contraceptivecontrol. AdmissionCriteria Admissionto the study was limited to women in good physical health, 18 to 35 years of age, who wanted to breastfeedtheir infant, who had a parity of 2-6 (includingcurrent delivery),and who could be followed up for 6 months. In addition,each woman's current pregnancymust have been full-term,with no major complicationsduring labor or delivery, and must have yielded only one infant. The infant must have been generallyhealthy at birth, with no major diseases or abnormalities. The infant'sexact weight at birth must have been known and must have been at least 2000 g. Finally, each woman must have satisfactorily breastfedat least one infant in the past for at least 4 months, with no history of puerperalmastitis, and planned to breastfeedher most
JULY 1991 VOL. 44 NO. 1
33
CONTRACEPTION recent infant for informed consent.
at least
6 months.
All
participating
women gave
Methods of Analysis Frequency measures were compared using standard uncorrected Chi-square tests. Mean values were compared using the Student’s t-test. Pregnancy and infant death rates were calculated using survival analysis. Rates for pregnancy were calculated using the estimated date of conception and were analyzed using the Lee-Desu statistic (9). Statistical significance was selected as a p-value of 0.05 or less. Therefore, the reader should assume that not significant is > 0.05. RESULTS Baseline Characteristics Maternal baseline characteristics such as age and breastfeeding history were similar between the POC and non-hormonal groups. Obstetric history variables such as total live births and number of previous infant deaths were also similar between the two groups. When previous use of contraception was compared between the two groups under study, it was found that significantly more women in the POC group reported using progestin-only pills while breastfeeding their previous child (5.4% of the women in the POC group vs. 0.4% of the women in the non-hormonal group, pc.01) . Also, significantly more women in the non-hormonal group reported using the IUD while breastfeedinq their previous child (33.5% of the women in the non-hormonal group vs. 14.1% of the women in the POC group, pc.001). Infant baseline characteristics were similar between the two groups with the exception of mean infant birth weight. The mean infant birth weight for the POC group was 3524 q versus 3455 q for the non-hormonal Mean infant height, mean infant head circumference, and group (pc.05). infant gender distribution were similar between the two groups. The non-hormonal methods chosen were the IUD, foam/diaphragm/jelly, condoms, and withdrawal/rhythm, with the majority of women (74.8%) choosing the IUD as their contraceptive method. Studv Terminations and Follow-up Wine women in the POC ctrouo and eiaht women in the non-hormonal arouo were excluded from the-anaiysis because they were above the protkol’s selection criteria limit for parity (parity 2-6). Of the remaining 483 women, 236 women in the POC group (97.9%) and 235 women in the non-hormonal group (97.1%) returned for at least one follow-up. The six-month follow-up rate was 84.6 for the POC group and 87.0 for the non-hormonal group. There were a total of five discontinuations during the study. One discontinuation occurred in the POC group (accidental pregnancy) and the other four discontinuations occurred in the non-hormonal group
34
JULY 1991 VOL. 44 NO. 1
CONTRACEPTION (1 accidental pregnancy, 3 infant deaths). The pregnancy in the POC group was attributed to user failure and occurred after the subject missed three consecutive pills. The pregnancy in the non-hormonal group occurred to an IUD user and was a normal intrauterine pregnancy. Both pregnancies occurred at the 5th month follow-up interval (based on the estimated date of conception). The cumulative life table pregnancy rate at 6 months was 0.5 for both The cumulative life table infant death rate at 6 months was groups. 0.0 for the POC group and 1.5 for the non-hormonal group. These differences were not statistically significant. Breastfeeding Patterns As shown in Table I, mean breastfeeding frequencies were similar between the POC and non-hormonal groups with the exception of the 5th month follow-up interval, where POC users reported significantly more breastfeeding episodes per 24 hours than non-hormonal users (pc.05). The mean duration of breastfeeding episodes was also reported at each follow-up and did not differ significantly between the two groups throughout the entire study. Table
I
Mean Frequency of Breastfeeding Episodes Per 24 Eours and Average Duration of Each Episode Follow-up Month
Mean Frequency Per 24 Hours Freq.
POC * S.D.
Non-Hormonal Freq. + S.D.
Mean Duration of Episodes (min) Freq.
POC + S.D.
Non-Hormonal Freq. + S.D.
1
7.2 r 1.0
7.3 f 0.8
17.9
+ 2.9
18.1
2
7.0 r 0.9
6.9 f 1.0
18.4
? 2.5
18.7 + 2.5
3
6.6 f 0.9
6.5 + 1.1
19.0
f 2.5
19.5 f 4.4
4
6.1 * 1.1
6.0 ?: 1.2
19.4
f 1.9
19.7
* 2.2
?: 1.3
5.3 k 1.6
19.7
2 1.9
19.9
f 2.2
5.1 f 1.5
5.0 f 1.5
19.9 * 2.0
19.9
f 2.3
5 6 *p < .05,
*5.7
using
t-test,
? 2.9
df=354
Maternal Assessment of Milk Production Changes in milk production were reported by the mothers at their follow-up visits and were based on their subjective assessment of their milk production since their last follow-up visit. There were only five
JULY 1991 VOL. 44 NO. 1
35
reports of increase in milk production. All reported increases were given at either the 1st or 2nd month follow-up visit and there was no significant difference between groups. Reports of decrease in milk were higher for the non-hormonal production, presented in Table II, group at each of the six monthly follow-ups, yet, only significantly higher at the 5th and 6th month follow-up intervals (p
A Comparative Study of a Progestin-Only Oral Contraceptive versus Non-Hormonal Methods in Lactating Womenin Buenos Aires, Argentina
Angel V. Moggia,lM.D.‘, Gena S. Harris B.A.zi Thomas R. Dunson, M.S.‘:, Ruben Diaz, M.D. , Maria Su?ana Moggia, M.D. , Miguel A. Ferrer, M.D. , and Susan L. McMullen, M.A.
I9 de Julio 39, Bernal 1876, Buenos Aires, Argentina Research Triangle Park, NC 27709 USA 2Family Health International,
ABSTRACT A non-randomized comparative clinical trial of the progestin-only oral contraceptive (POC), Ovrette (75 mcg norgestrel) (Wyeth), versus non-hormonal methods was conducted at two clinics in Buenos Aires, Argentina. The trial was designed to assess the breastfeeding patterns of women choosing progestin-only oral contraception and non-hormonal methods of contraception, and to study the relationship between lactation and the clinical performance of a POC. Five-hundred women were allocated to either the progestin-only pill group (n = 250) or to the non-hormonal group (n = 250) and were followed up monthly for six months after admission. Measurements in mean infant weight, mean infant length, and mean head circumference were similar throughout the follow-up period. Non-hormonal users reported significantly more self-perceived decreases in milk production at the 5th and 6th month follow-up intervals. Acceptance and continued use of the pill were excellent, with only one womandiscontinuing because of a pregnancy The principal side effect which was attributed to user failure. reported by women in both groups was intermenstrual bleeding. *To whomrequests
for reprints
should be sent.
Submitted for publication January 31, 1991 Accepted for publication May 1, 1991
JULY 1991 VOL. 44 NO. 1
31
CONTRACEPTION INTRODUCTION During the postpartum period, prevention of pregnancy is important because birth spacings of two years or more results in significantly better infant and maternal health (l), because of the adverse effect pregnancy has on lactation (2), and because of the desire/need for limitation of family size. The immediate postpartum period is assumed to be a time when many women are receptive to family planning information and services. There is some concern about which contraceptive methods are most appropriate in the postpartum period, particularly for lactating women. In many countries, lactation is the infant’s only source of nutrition Some women, including those who are and protection against infection. breastfeeding their infants, prefer oral contraceptives. Yet there is concern about use of combined oral contraceptives during lactation because many studies have shown that lactation may be impaired by combined estrogen-progestin oral contraceptives (perhaps even those with relatively low doses of estrogen) (3-6). While the establishment of lactation may not be affected by these hormones, milk production, once established, frequently declines and lactation may cease On the other hand, previous research indicates that the prematurely. use of progestin-only oral contraceptives (POCs) during lactation does not appear to have adverse effects on lactation or infant growth and may even enhance lactation (5,7,8) . This study was designed to assess the breastfeeding patterns of women choosing progestin-only oral contraception and non-hormonal methods of contraception, and to study the relationship between lactation and the clinical performance of a POC. Two of the primary over time objectives in this study were to compare: (a) the difference in the weight of breastfed infants, and (b) the duration of and the unsupplemented breast feeding (i. e . , time to supplementation) duration of all breastfeeding (i.e., supplemented and unsupplemented breastfeeding) between women who used the progestin-only pill and women who did not use hormonal methods. As a third objective, the progestin-only group was evaluated for the acceptance and continued use of the pill. Also, the side effects experienced by women while taking the progestin-only pill were assessed and compared to those side effects experienced by women using non-hormonal methods. SUBJECTSAND METHODS Study Design From October 1985 to June 1987, women were admitted to two clinics in Buenos Aires, Argentina, the Jose Penna Hospital and the Policlinico Bernal. Two-hundred-fifty women were allocated to the progestin-only oral contraceptive group and 250 women were allocated to the non-hormonal contraceptive group. Women were asked to choose contraception and an array
32
between low-dose progestin-only of non-hormonal contraception.
oral Choice
of
JULY 1991 VOL. 44 NO. 1
CONTRACEPTION contraceptionwas not randomized. Women who elected non-hormonal methods were asked to give their reasons for not accepting progestin-onlypills: this was used as a measure of acceptability(or lack thereof) of POCs. Enrollmentin the study and initiationof pill use began within one week after delivery. Early initiationof pill use was chosen for two reasons. Early initiationmay be desirablein some settingswhere delivery is the only time a woman is in contact with the health care system. Therefore,it is importantto determinewhether such early initiationaffects the establishmentof lactation. Secondly,if no adverse effects of early initiationwere found in the study, then it would be unlikelythat later initiationwould be detrimental (7). For women who chose to use the IUD, the devices were insertedwithin one week postpartumand usually towards the end of that week, thus closely parallelingearly pill initiation. The other coitus-related methods chosen were all initiatedwhenever coitus was resumed. All of the women were breastfeedingat the time of admission. Women were asked to breastfeedevery three hours with an intervalbetween the last one at night and the first one of the followingday. The women in this study were given no additionalcounselingor support in breastfeeding,other than that which was normally given to breastfeedingmothers. Infantswere weighed and measured at admissionand at each of six monthly follow-upvisits. Breastfeedingepisodes and bleeding patterns reportedby the women at their f.ollow-up visits were based on retrospectiverecall. Bleeding pattern reports were based on the subjectiveinterpretationof each woman, and not from bleeding records or other objectivemeasures. Oral ContraceptiveEvaluated The progestin-onlypill supplied in this study, Ovrette (Wyeth, Philadelphia,PA), is composedof 75 mcg norgestreland is provided in 28-day packages. All pills contain active ingredientsand must be taken daily for proper contraceptivecontrol. AdmissionCriteria Admissionto the study was limited to women in good physical health, 18 to 35 years of age, who wanted to breastfeedtheir infant, who had a parity of 2-6 (includingcurrent delivery),and who could be followed up for 6 months. In addition,each woman's current pregnancymust have been full-term,with no major complicationsduring labor or delivery, and must have yielded only one infant. The infant must have been generallyhealthy at birth, with no major diseases or abnormalities. The infant'sexact weight at birth must have been known and must have been at least 2000 g. Finally, each woman must have satisfactorily breastfedat least one infant in the past for at least 4 months, with no history of puerperalmastitis, and planned to breastfeedher most
JULY 1991 VOL. 44 NO. 1
33
CONTRACEPTION recent infant for informed consent.
at least
6 months.
All
participating
women gave
Methods of Analysis Frequency measures were compared using standard uncorrected Chi-square tests. Mean values were compared using the Student’s t-test. Pregnancy and infant death rates were calculated using survival analysis. Rates for pregnancy were calculated using the estimated date of conception and were analyzed using the Lee-Desu statistic (9). Statistical significance was selected as a p-value of 0.05 or less. Therefore, the reader should assume that not significant is > 0.05. RESULTS Baseline Characteristics Maternal baseline characteristics such as age and breastfeeding history were similar between the POC and non-hormonal groups. Obstetric history variables such as total live births and number of previous infant deaths were also similar between the two groups. When previous use of contraception was compared between the two groups under study, it was found that significantly more women in the POC group reported using progestin-only pills while breastfeeding their previous child (5.4% of the women in the POC group vs. 0.4% of the women in the non-hormonal group, pc.01) . Also, significantly more women in the non-hormonal group reported using the IUD while breastfeedinq their previous child (33.5% of the women in the non-hormonal group vs. 14.1% of the women in the POC group, pc.001). Infant baseline characteristics were similar between the two groups with the exception of mean infant birth weight. The mean infant birth weight for the POC group was 3524 q versus 3455 q for the non-hormonal Mean infant height, mean infant head circumference, and group (pc.05). infant gender distribution were similar between the two groups. The non-hormonal methods chosen were the IUD, foam/diaphragm/jelly, condoms, and withdrawal/rhythm, with the majority of women (74.8%) choosing the IUD as their contraceptive method. Studv Terminations and Follow-up Wine women in the POC ctrouo and eiaht women in the non-hormonal arouo were excluded from the-anaiysis because they were above the protkol’s selection criteria limit for parity (parity 2-6). Of the remaining 483 women, 236 women in the POC group (97.9%) and 235 women in the non-hormonal group (97.1%) returned for at least one follow-up. The six-month follow-up rate was 84.6 for the POC group and 87.0 for the non-hormonal group. There were a total of five discontinuations during the study. One discontinuation occurred in the POC group (accidental pregnancy) and the other four discontinuations occurred in the non-hormonal group
34
JULY 1991 VOL. 44 NO. 1
CONTRACEPTION (1 accidental pregnancy, 3 infant deaths). The pregnancy in the POC group was attributed to user failure and occurred after the subject missed three consecutive pills. The pregnancy in the non-hormonal group occurred to an IUD user and was a normal intrauterine pregnancy. Both pregnancies occurred at the 5th month follow-up interval (based on the estimated date of conception). The cumulative life table pregnancy rate at 6 months was 0.5 for both The cumulative life table infant death rate at 6 months was groups. 0.0 for the POC group and 1.5 for the non-hormonal group. These differences were not statistically significant. Breastfeeding Patterns As shown in Table I, mean breastfeeding frequencies were similar between the POC and non-hormonal groups with the exception of the 5th month follow-up interval, where POC users reported significantly more breastfeeding episodes per 24 hours than non-hormonal users (pc.05). The mean duration of breastfeeding episodes was also reported at each follow-up and did not differ significantly between the two groups throughout the entire study. Table
I
Mean Frequency of Breastfeeding Episodes Per 24 Eours and Average Duration of Each Episode Follow-up Month
Mean Frequency Per 24 Hours Freq.
POC * S.D.
Non-Hormonal Freq. + S.D.
Mean Duration of Episodes (min) Freq.
POC + S.D.
Non-Hormonal Freq. + S.D.
1
7.2 r 1.0
7.3 f 0.8
17.9
+ 2.9
18.1
2
7.0 r 0.9
6.9 f 1.0
18.4
? 2.5
18.7 + 2.5
3
6.6 f 0.9
6.5 + 1.1
19.0
f 2.5
19.5 f 4.4
4
6.1 * 1.1
6.0 ?: 1.2
19.4
f 1.9
19.7
* 2.2
?: 1.3
5.3 k 1.6
19.7
2 1.9
19.9
f 2.2
5.1 f 1.5
5.0 f 1.5
19.9 * 2.0
19.9
f 2.3
5 6 *p < .05,
*5.7
using
t-test,
? 2.9
df=354
Maternal Assessment of Milk Production Changes in milk production were reported by the mothers at their follow-up visits and were based on their subjective assessment of their milk production since their last follow-up visit. There were only five
JULY 1991 VOL. 44 NO. 1
35
reports of increase in milk production. All reported increases were given at either the 1st or 2nd month follow-up visit and there was no significant difference between groups. Reports of decrease in milk were higher for the non-hormonal production, presented in Table II, group at each of the six monthly follow-ups, yet, only significantly higher at the 5th and 6th month follow-up intervals (p
