CONTRACEPTION
POSTPONEMENT CONTRACEPTIVE
OF
WITHDRAWAL BLEEDING WITH A MONOPHASIC ORAL CONTAINING DESOGESTREL AND ETRINYLESTRADIOL
W. S. de Voogd Medical Department Organon Nederland B.V. oss, The Netherlands Abstract This study investigated the ability of a monophasic contraceptive, containing desogestrel sub-50 oral and to postpone withdrawal bleeding in normal ethinylestradiol, healthy women. In the analyzed group of 105 regular users about 75% did not experience any vaginal of Marvelon, of postponement. bleeding during the 21 days A 95% confidence interval was calculated which suggests that the percentage of women able to postpone their withdrawal bleeding successfully for 19 days ranges between 67.0% and Women with no vaginal blood loss in the postponement 83.5%. period were more willing to try this method of postponement again, compared to women who experienced vaginal blood loss period. This difference in the postponement was statistically significant. Nevertheless, the majority of women with vaginal blood loss were also willing to try this method again if necessary. The study results suggest that offers an effective and acceptable Marvelon method of for three weeks for most postponing withdrawal bleeding regular users of this contraceptive. Introduction The use of hormonal preparations to delay menses is well known. In non-oral contraceptive users, menses delay achieved in several ways. can be First of all, a progestagen preparation or a combination of a progestagen and an estrogen can be administered in the luteal phase of the cycle. Another possibility is the administration of ovulation inhibitors starting in the follicular phase of the menstrual cycle. In regular oral contraceptive users, postponement of withdrawal bleeding can be achieved by skipping the tablet-free period between two consecutive pill Although widely practised, only few experimental strips. the results are available in literature concerning postponement of withdrawal bleeding in regular oral Submitted for publication May 7, 1991 Accepted for publication May 31, 1991
AUGUST
1991 VOL. 44 NO. 2
107
CONTRACEPTION
These studies describe the results of contraceptive users. a 50 pg ethinylestradiol-containing preparation (l), as well In the current study, a as some sub-50 preparations (2,3). sub-50 monophasic oral contraceptive was investigated for ability to postpone vaginal bleeding for a maximum its period of 21 days.
Materials
and Methods
The oral contraceptive under investigation was a desogestrel/ethinylestradiol preparation monophasi (Marvelon E /Organon). The composition of this contraceptive is 0.150 mg desogestrel + 0.030 mg ethinylestradiol per tablet. The normal dosage regimen is the use of 1 tablet per day for 21 consecutive days followed by a tablet-free period of 7 days. In total, 21 Dutch general practitioners participated in the study. Each physician was asked to recruit 6 women according to an inclusion/exclusion checklist. The women had to be regular Marvelon users for at least 6 months. They were asked to postpone their withdrawal bleeding by skipping the tablet-free period and continue their daily tablet intake for another 21 days. During these last 21 the women noted on a diary card their tablet intake days, and whether any vaginal bleeding was experienced or not. No distinction was made between spotting and breakthrough Furthermore, the volunteers were asked whether bleeding. they were willing to use this method again if necessary. In the analysis, the first day of bleeding was taken as reference. A cumulative percentage was the point of calculated over 21 days for women who did not experience any vaginal bleeding. Confidence limits were calculated according to the formula of Greenwood. The answers to the question concerning future use of this method of postponement were tabulated. Differences in answers between 'bleeders' 'non-bleeders' and were statistically analyzed using the Fisher's exact test (2-tailed). Results The 21 participating general practitioners presented data concerning 116 women. Data from 11 volunteers were analysis because of excluded from the major protocol violations (incomplete data, tablet intake failure). The volunteers on first average age of the the day of postponement was 24.6 years (median 23.4 years). The age distribution of the study population is given in Figure 1. At least one bleeding day was experienced by 10 women in the first week, 10 women in the second week and 6 women in the third week of the postponement period. The cumulative percentage of women who did not experience any vaginal In this study, about 75% of bleeding is shown in Figure 2.
108
AUGUST
I!391 VOL. 44 NO. 2
CONTRACEPTION
Number of volunteers ,0
1
I
I II
I I
24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42
19
Age in years
Fig. 1. Age distribution of the study population on the first day of postponement of withdrawal bleeding (n=105).
100
Percentage non-b?:eders 90 80-
70-
600 10-
1
2
3
4
5
6
i
6
9
1 IC li 12 13 14 15 16 17 16 19 20 21
Day of postponementof withdrawal bleeding Fig. 2. Cumulative percentage of volunteers without any vaginal bleeding in the study period.
AUGUST
1991 VOL. 44 NO. 2
109
CONTRACEPTION
the volunteers were able to completely postpone withdrawal Table I shows the calculated 95% bleeding for 21 days. limits for several days of the postponement confidence These confidence limits suggest that the percentage period. of women able to postpone their withdrawal bleeding with the study drug for 7 days ranges between 84.9-96.1%, for I4 days between 73.4~88.5% and for 19 days between 67.0-83.5%. The answers of the volunteers to the question whether this use method of again if they would postponement necessary are shown in Table II. Of the total analyzable 91 volunteers answered with 'yes', 9 with study population, did not answer this question. 'no' and 5 women In the subpopulation of 'non-bleeders', 75 volunteers answered 'yes', 2 with 'no' and 2 women did not answer the question, in the subpopulation of 'bleeders', while 16 volunteers answered with 'yes', 7 with 'no' and 3 women did not answer For the statistical analyses, the numbers of the question. the 'no answer given'-group were pooled with the 'yes'-group or were excluded. or with the 'no'-group The differences in answers between the 'non-bleeders'-group and 'bleeders'statistically significantly different in all group were cases (Fisher's Exact Test, pCO.05). Finally, 39 out of the 105 evaluated volunteers used co-medication in the last two menstrual cycles and/or during In the subgroup of women who the postponement period. experienced vaginal bleeding, no co-medication was used that is known to be able to influence the plasma levels of the steroid hormones contained in oral contraceptives. On the in the subgroup of 'non-bleeders', 1 woman did other hand, take amoxicillin and 2 women used active carbon during the postponement period. Discussion The objective of the study was to determine the success rate of postponement of withdrawal bleeding in at least 100 The results suggest that the women already using Marvelon. will majority of such women successfully achieve postponement of their withdrawal bleeding for 21 days without any vaginal bleeding problems. In the study of Hamerlynck et al. (3), a cumulative percentage of vaginal blood loss, including the 21 days postponement period, was preceding the presented for When corrected for these first 21 Marvelon users (n=29). it can be estimated that approximately 37% of the days, subpopulation (n=24) experienced remaining Marvelon user blood loss in the postponement period. vaginal This subpopulation consisted of women who did not experience any vaginal bleeding in the preceding 21 days. In the current percentage of the 'bleeders' in the study (n=105), postponement period was about 25%. It is not known how many
110
AUGUST
1991 VOL. 44 NO. 2
CONTRACEPTION
Table I.
95% Confidence intervals postponement period
Percentage non-bleeders
Day of lostponement
Table
II.
Confidence lower limit %
interval UPPer limb %
3
97.1
94.0
100.0
5
94.3
89.8
98.7
6
91.4
06.1
96.6
7
90.5
64.9
96.1
62.5
94.7
6
66.6
11
85.7
79.0
92.4
12
82.9
75.6
90.1
13
81.9
74.5
89.3
14
81.0
73.4
88.5
15
80.0
72.3
87.7
16
79.0
71.3
86.8
17
77.1
69.1
85.2
18
76.2
68.0
84.3
19
75.2
67.0
83.5
Answers on the question, whether the woman willing to use this method of postponement withdrawal bleeding again, if necessary
Non-bleeders
AUGUST
for several days of the
Bleeders
Total
Yes
75
16
91
No
2
7
9
No answer given
2
3
5
1991 VOL. 44 NO. 2
was of
111
CONTRACEPTION
of these preceding
women had 21 days.
experienced
vaginal
bleeding
in
the
Bleeding in the postponement period influenced the willingness of the women to use this method of postponement again. Nevertheless, it was a surprising finding that the majority of the 'bleeders' were still willing to try this method again if necessary. Hamerlynck et a1.(3) studied the acceptability of this method of postponing withdrawal bleeding and observed a comparable attitude. It seems that the occurrence of blood loss, although unwanted, is quite acceptable to women. This might these reflect some ambivalence between the belief in the need for a monthly bleeding and the desire to manipulate the actual time of the withdrawal bleeding. A source of this ambivalence could be the relatively poor understanding of the oral contraceptive pill and/or withdrawal bleeding. In this respect, the study of Rutter et al. (4) in Australian women is relevant. In this study, more than 80% of the study population believed that it was necessary to experience monthly bleeding. On the other hand, about the same percentage of young women would prefer a much longer bleeding-free interval if a safe and reversible method was available. In conclusion, the current study results suggest that Marvelon offers an effective and acceptable method of postponing withdrawal bleeding for three weeks in most regular users of this contraceptive. Acknowledgements word of A appreciation is directed towards the participating general practitioners for their cooperation and to Ir. H. Rietbergen, Organon International B.V., for his statistical advice. References 1.
2.
3.
4.
112
Loudon NB, Foxwell M, Potts DM, Guild AL, Short RV. Acceptability of an oral contraceptive that reduces the frequency of menstruation: the tri-cycle pill regimen. Brit Med J 1977;2:487-90. Vollebregt JA, Doornebos CM, Hamerlynck JV. A study on postponement of menses with low-dose combined oral contraceptives - Outcome and acceptability. Adv Contracept 1985;1:207. Hamerlynck JVThH, Vollebregt JA, Doornebos CM, Muntendam P. Postponement of withdrawal bleeding in women using low-dose combined oral contraceptives. Contraception 1987;35:199-205. Rutter W, Knight C, Vizzard J, Mira M, Abraham S. Women's attitudes to withdrawal bleeding and their and beliefs about the oral contraceptive knowledge Med J Austr 1988;149:417-19. pill.
AUGUST
1991 VOL. 44 NO. 2
POSTPONEMENT CONTRACEPTIVE
OF
WITHDRAWAL BLEEDING WITH A MONOPHASIC ORAL CONTAINING DESOGESTREL AND ETRINYLESTRADIOL
W. S. de Voogd Medical Department Organon Nederland B.V. oss, The Netherlands Abstract This study investigated the ability of a monophasic contraceptive, containing desogestrel sub-50 oral and to postpone withdrawal bleeding in normal ethinylestradiol, healthy women. In the analyzed group of 105 regular users about 75% did not experience any vaginal of Marvelon, of postponement. bleeding during the 21 days A 95% confidence interval was calculated which suggests that the percentage of women able to postpone their withdrawal bleeding successfully for 19 days ranges between 67.0% and Women with no vaginal blood loss in the postponement 83.5%. period were more willing to try this method of postponement again, compared to women who experienced vaginal blood loss period. This difference in the postponement was statistically significant. Nevertheless, the majority of women with vaginal blood loss were also willing to try this method again if necessary. The study results suggest that offers an effective and acceptable Marvelon method of for three weeks for most postponing withdrawal bleeding regular users of this contraceptive. Introduction The use of hormonal preparations to delay menses is well known. In non-oral contraceptive users, menses delay achieved in several ways. can be First of all, a progestagen preparation or a combination of a progestagen and an estrogen can be administered in the luteal phase of the cycle. Another possibility is the administration of ovulation inhibitors starting in the follicular phase of the menstrual cycle. In regular oral contraceptive users, postponement of withdrawal bleeding can be achieved by skipping the tablet-free period between two consecutive pill Although widely practised, only few experimental strips. the results are available in literature concerning postponement of withdrawal bleeding in regular oral Submitted for publication May 7, 1991 Accepted for publication May 31, 1991
AUGUST
1991 VOL. 44 NO. 2
107
CONTRACEPTION
These studies describe the results of contraceptive users. a 50 pg ethinylestradiol-containing preparation (l), as well In the current study, a as some sub-50 preparations (2,3). sub-50 monophasic oral contraceptive was investigated for ability to postpone vaginal bleeding for a maximum its period of 21 days.
Materials
and Methods
The oral contraceptive under investigation was a desogestrel/ethinylestradiol preparation monophasi (Marvelon E /Organon). The composition of this contraceptive is 0.150 mg desogestrel + 0.030 mg ethinylestradiol per tablet. The normal dosage regimen is the use of 1 tablet per day for 21 consecutive days followed by a tablet-free period of 7 days. In total, 21 Dutch general practitioners participated in the study. Each physician was asked to recruit 6 women according to an inclusion/exclusion checklist. The women had to be regular Marvelon users for at least 6 months. They were asked to postpone their withdrawal bleeding by skipping the tablet-free period and continue their daily tablet intake for another 21 days. During these last 21 the women noted on a diary card their tablet intake days, and whether any vaginal bleeding was experienced or not. No distinction was made between spotting and breakthrough Furthermore, the volunteers were asked whether bleeding. they were willing to use this method again if necessary. In the analysis, the first day of bleeding was taken as reference. A cumulative percentage was the point of calculated over 21 days for women who did not experience any vaginal bleeding. Confidence limits were calculated according to the formula of Greenwood. The answers to the question concerning future use of this method of postponement were tabulated. Differences in answers between 'bleeders' 'non-bleeders' and were statistically analyzed using the Fisher's exact test (2-tailed). Results The 21 participating general practitioners presented data concerning 116 women. Data from 11 volunteers were analysis because of excluded from the major protocol violations (incomplete data, tablet intake failure). The volunteers on first average age of the the day of postponement was 24.6 years (median 23.4 years). The age distribution of the study population is given in Figure 1. At least one bleeding day was experienced by 10 women in the first week, 10 women in the second week and 6 women in the third week of the postponement period. The cumulative percentage of women who did not experience any vaginal In this study, about 75% of bleeding is shown in Figure 2.
108
AUGUST
I!391 VOL. 44 NO. 2
CONTRACEPTION
Number of volunteers ,0
1
I
I II
I I
24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42
19
Age in years
Fig. 1. Age distribution of the study population on the first day of postponement of withdrawal bleeding (n=105).
100
Percentage non-b?:eders 90 80-
70-
600 10-
1
2
3
4
5
6
i
6
9
1 IC li 12 13 14 15 16 17 16 19 20 21
Day of postponementof withdrawal bleeding Fig. 2. Cumulative percentage of volunteers without any vaginal bleeding in the study period.
AUGUST
1991 VOL. 44 NO. 2
109
CONTRACEPTION
the volunteers were able to completely postpone withdrawal Table I shows the calculated 95% bleeding for 21 days. limits for several days of the postponement confidence These confidence limits suggest that the percentage period. of women able to postpone their withdrawal bleeding with the study drug for 7 days ranges between 84.9-96.1%, for I4 days between 73.4~88.5% and for 19 days between 67.0-83.5%. The answers of the volunteers to the question whether this use method of again if they would postponement necessary are shown in Table II. Of the total analyzable 91 volunteers answered with 'yes', 9 with study population, did not answer this question. 'no' and 5 women In the subpopulation of 'non-bleeders', 75 volunteers answered 'yes', 2 with 'no' and 2 women did not answer the question, in the subpopulation of 'bleeders', while 16 volunteers answered with 'yes', 7 with 'no' and 3 women did not answer For the statistical analyses, the numbers of the question. the 'no answer given'-group were pooled with the 'yes'-group or were excluded. or with the 'no'-group The differences in answers between the 'non-bleeders'-group and 'bleeders'statistically significantly different in all group were cases (Fisher's Exact Test, pCO.05). Finally, 39 out of the 105 evaluated volunteers used co-medication in the last two menstrual cycles and/or during In the subgroup of women who the postponement period. experienced vaginal bleeding, no co-medication was used that is known to be able to influence the plasma levels of the steroid hormones contained in oral contraceptives. On the in the subgroup of 'non-bleeders', 1 woman did other hand, take amoxicillin and 2 women used active carbon during the postponement period. Discussion The objective of the study was to determine the success rate of postponement of withdrawal bleeding in at least 100 The results suggest that the women already using Marvelon. will majority of such women successfully achieve postponement of their withdrawal bleeding for 21 days without any vaginal bleeding problems. In the study of Hamerlynck et al. (3), a cumulative percentage of vaginal blood loss, including the 21 days postponement period, was preceding the presented for When corrected for these first 21 Marvelon users (n=29). it can be estimated that approximately 37% of the days, subpopulation (n=24) experienced remaining Marvelon user blood loss in the postponement period. vaginal This subpopulation consisted of women who did not experience any vaginal bleeding in the preceding 21 days. In the current percentage of the 'bleeders' in the study (n=105), postponement period was about 25%. It is not known how many
110
AUGUST
1991 VOL. 44 NO. 2
CONTRACEPTION
Table I.
95% Confidence intervals postponement period
Percentage non-bleeders
Day of lostponement
Table
II.
Confidence lower limit %
interval UPPer limb %
3
97.1
94.0
100.0
5
94.3
89.8
98.7
6
91.4
06.1
96.6
7
90.5
64.9
96.1
62.5
94.7
6
66.6
11
85.7
79.0
92.4
12
82.9
75.6
90.1
13
81.9
74.5
89.3
14
81.0
73.4
88.5
15
80.0
72.3
87.7
16
79.0
71.3
86.8
17
77.1
69.1
85.2
18
76.2
68.0
84.3
19
75.2
67.0
83.5
Answers on the question, whether the woman willing to use this method of postponement withdrawal bleeding again, if necessary
Non-bleeders
AUGUST
for several days of the
Bleeders
Total
Yes
75
16
91
No
2
7
9
No answer given
2
3
5
1991 VOL. 44 NO. 2
was of
111
CONTRACEPTION
of these preceding
women had 21 days.
experienced
vaginal
bleeding
in
the
Bleeding in the postponement period influenced the willingness of the women to use this method of postponement again. Nevertheless, it was a surprising finding that the majority of the 'bleeders' were still willing to try this method again if necessary. Hamerlynck et a1.(3) studied the acceptability of this method of postponing withdrawal bleeding and observed a comparable attitude. It seems that the occurrence of blood loss, although unwanted, is quite acceptable to women. This might these reflect some ambivalence between the belief in the need for a monthly bleeding and the desire to manipulate the actual time of the withdrawal bleeding. A source of this ambivalence could be the relatively poor understanding of the oral contraceptive pill and/or withdrawal bleeding. In this respect, the study of Rutter et al. (4) in Australian women is relevant. In this study, more than 80% of the study population believed that it was necessary to experience monthly bleeding. On the other hand, about the same percentage of young women would prefer a much longer bleeding-free interval if a safe and reversible method was available. In conclusion, the current study results suggest that Marvelon offers an effective and acceptable method of postponing withdrawal bleeding for three weeks in most regular users of this contraceptive. Acknowledgements word of A appreciation is directed towards the participating general practitioners for their cooperation and to Ir. H. Rietbergen, Organon International B.V., for his statistical advice. References 1.
2.
3.
4.
112
Loudon NB, Foxwell M, Potts DM, Guild AL, Short RV. Acceptability of an oral contraceptive that reduces the frequency of menstruation: the tri-cycle pill regimen. Brit Med J 1977;2:487-90. Vollebregt JA, Doornebos CM, Hamerlynck JV. A study on postponement of menses with low-dose combined oral contraceptives - Outcome and acceptability. Adv Contracept 1985;1:207. Hamerlynck JVThH, Vollebregt JA, Doornebos CM, Muntendam P. Postponement of withdrawal bleeding in women using low-dose combined oral contraceptives. Contraception 1987;35:199-205. Rutter W, Knight C, Vizzard J, Mira M, Abraham S. Women's attitudes to withdrawal bleeding and their and beliefs about the oral contraceptive knowledge Med J Austr 1988;149:417-19. pill.
AUGUST
1991 VOL. 44 NO. 2
