Acceptability and Clinical Effectivity of the Oral Progestogens for Fertility Control in Indian Women

Transcription

1 Acceptability and Clinical Effectivity of the Oral Progestogens for Fertility Control in Indian Women PRABHAKER N. SHAH, M.D., F.C.P.S. EVEN IN ADVANCED countries today, the practice of family planning methods is primarily female oriented. The corollary, therefore, is that the use of only such methods that are acceptable to women in a given population could have an impact on reduction in birth rate. Again, for an impressive reduction, it is not merely the extent to which a given population uses the contraceptives but perhaps more important is the efficiency of the methods used by them. Using this information on Western population, Sheps and Perrin (as quoted by Chandrasekharan) 6 have shown that the use of contraceptives by 90% of the population with 50% effectiveness will reduce the birth rate by 18%, while their use by 50% of the population with 90% effectiveness will reduce the birth rate by 34%. Therefore, it is important to discover first, the use-effectiveness of the various methods employed by our women. CHOICE OF METHODS The compiled data on the efficacy of the various methods used by couples mostly belonging to the low socioeconomic level in the city of Bombay, are summarized in Table l. If no methods at all were used, the expected pregnancy rate, as reported by Israel, would be 77 pregnancies per 100 women-years, while with all the available methods there is slight to almost From the Department of Endocrinology, Indian Cancer Research Center, Parel, Bombay 12, India. Presented at the Third Annual Meeting of the Indian Society for the Study of Reproduction at Chandigarh, Dec. 6-7, The author wishes to acknowledge the help given by the social worker, Miss Surinder Kaur Kharbanda, in the study of the preference of the method by the "cafeteria" approach. The author also wishes to acknowledge the generous supply of Anovlar received from Schering Asia GmBH, of Enavid E and various formulations of ethynodiol diacetate provided by G. D. Searle & Co. Ltd. 286

2 VOL. 19, No.2, 1968 ORAL PROGESTOGENS 287 TABLE 1. Clinical Studies Employing Various Contraceptive Methods Aggregate Pregnancies/ Couples time used 100 women- Method (No.) (Mo.) years Author Foam tablets Israel 3 Diaphra~m & jelly Israe!S Condom Shah 7 IUD LC.M.R., 1966 Oral pill Shah 7 100% effectiveness in controlling birth rates. It is evident from these data that the use of conventional methods such as foam tablets or diaphragm and jelly should be strongly deprecated, and methods such as condom, IUD, and oral pill should be advocated for the national family planning program. The pregnancy-rate figure using IUD was obtained from the Contraceptive Testing Unit at the Indian Cancer Research Centre (I.C.M.R.) as our present data on IUD are still too small for comparison. The extraordinary use-effectiveness of the oral pill method is demonstrated by the pregnancy rate of 0.12 per 100 women-years. To determine the acceptability of the aforementioned methods by this group of population, one of our social workers studied the preference of the method in 200 consecutive subjects by displaying all the methods to them. Their preference by this "cafeteria" approach is as shown in Table 2. Of the 200 subjects, selection of a method was done by the wife alone in 168 instances while either the husband or the couple decided in the remaining 32 instances. It may be of interest to know that whenever the husband was present, he dominated in the selection of a method. On the other hand, whenever the wife alone was present, not infrequently, she appeared to prefer a method that could be used by the husband. Since our emphasis is on the attitude of the female, for further discussion, we will concern ourselves with this comparatively larger group of 168 women. It TABLE 2. Selection of Contraceptive Methods by Consecutive Couples Using "Cafeteria" Approach Methods Participant Total (No.) Jelly D &J* Condom IUD Oral pill Wife HUBband Both TOTAL * Diaphragm and jelly.

3 288 SHAH FERTILITY & STERILITY is evident here that 1 out of 3 (35.7%) women wanted the oral pill, while 1 out of 5 selected the IUD (22%). As aforesaid, selection of condom by the wife (30.9%) is biased and therefore cannot be taken seriously, since about 50% of the husbands did not cooperate to use the condom which was selected by their wives. Once the method was selected, the merits and demerits of methods were explained before giving the material for use, and the subject was permitted to change her mind if she so desired. It is necessary to state that 44 out of 168 women, after initial selection, dropped out of the study without accepting any method for use. Table 3 summarizes the results on the postexplanation acceptance of the method by the remaining 124 women. From this it is clear that 84 out of 124 women accepted-and used satisfactorily-the method they initially selected while the remaining 40, after explanation, changed to other methods. Of the 40 women who switched to another method, 21 preferred an oral pill and 7, an IUD. Thus, of the 124 women who accepted and used some method satisfactorily for a minimal period of 1 year, oral pill acceptance was far better than the condom or IUD, respectively, in order of frequency. Table 4 shows the analysis of change-over methods in the 40 women. From this it appears that once the husband decided not to use the condom, the wife by and large preferred to employ an efficient method. Again, perhaps for the same reason, the majority of those who initially selected the IUD, converted to the oral pill. There were, however, 5 exceptions to this who, after initial selection of the oral pill, felt that it was too much of a TABLE 3. Postexplanation Dropout and Acceptance of Methods Contraceptive method Subjects (No.) Jelly D&J* Condom IUD Oral pill DROPOUT SUBJECTS ACCEPTANCE SUBJECTS Used initially selected method Used other than initially selected method 40 5 ] TOTAL % 20.9% 43.5% * Diaphragm and jelly.

4 VOL. 19, No.2, 1968 ORAL PROGESTOGENS 289 TABLE 4. Exchange of Contraceptive Methods After Explanation Initially selected Method accepted after explanation Method Patients (No.) Jelly D &J* Condom IUD Oral pill Jelly D &J* 1 1 Condom IUD Oral pill TOTAL * Diaphragm and jelly. bother to take a pill every day and, therefore, accepted other methods. In brief, from these small data, it appears that 6 out of 10 women preferred to have 1 of the 2 recently available efficient methods-oral pill or IUDand about 2 of the remaining 4 women's husbands were willing to rely on condoms for contraception. PILL EFFECTIVENESS AND ACCEPTABILITY The various composition of the pills used in our series, their dosage, the method of administration, and the total number of cycles of medication are given in Table 5. The schedule described under the combined method conveys that both progesterone and estrogen are given from Day 5 to Day 24 in all 20 pills, while in the sequential method, estrogen alone is given for the first 10 days and then progesterone is given in addition to estrogen for the remaining 10 days. The 3 progestational compounds are given at different dose levels; of these, ethynodiol diacetate (ED) is given in low-dosage in both combined, as well as sequential schedules. It is pertinent to mention that we have used ED in half strength or in quarter strength of what has been marketed in the U.K. as an oral contraceptive, and these daily low doses appear to be satisfactory to our women. The 10/10 sequential schedule was conceived and employed by us as far back as 1963 and, thus far, we have had 331 satisfied users on this schedule, which appears to produce a physiologic type of endometrium and withdrawal bleeding. 5 The latter effect is a point of greater satisfaction to our women who, for several generations, have been conditioned to the idea that regularity of the cycle with a good flow equates with the degree of a woman's health. It is necessary to mention that with almost all the combined pills, the change in flow is in the direction of scantiness and this is a matter of great concern to the users.4 Our results with the sequential

5 290 SHAH FERTILITY & STERILITY 0.5 mg. are encouraging and to the present time, no pregnancy has occurred, in contrast with the experience in other countries where the sequential (15/5-6) schedule has been less consistently effective than the combined schedule. 1 2 One, therefore, wonders whether the success of this small dosage in Indian women is due to more effective 10/10 schedule or has any relation to the average lower body weight of our women (average weight, 40 kg.). We have also tried this compound in smaller dosage (0.25 mg.) both in combined and sequential (10/10) schedules. Although the combined 0.25 schedule has, so far, resulted in no pregnancies, the cyclic control is not as satisfactory as it is with the combined 0.5 mg. schedule. The first cycle breakthrough bleeding (BTB) with the former runs as high as 22%. Our preliminary results with sequential 0.25 in 50 women who completed 350 cycles are encouraging, but it is still too early to comment on this dosage. TABLE 5. Outline of Methods of Administration Compounds Mg. Tmde name Cycles of medication (No.) Norethisterone acetate + Ethinyl Estradiol N orethynodrol + EDt + EDt + EDt + EDt + * Ethinyl estradiol-3-methyl-ether. t Ethynodiol diacetate. COMBINED SEQUENTIAL Anovlar Enovid E

6 VOL. 19, No.2, 1968 ORAL PROGESTOGENS 291 TABLE 6. Dropout Due to Reasons Unrelated to Drug Reasons No. % Planned pregnancy 64 l 37.7 Illness, separation, death, sterilization 33 f Moved away 87[ 36.5 Tablets taken from other sources 7 f Advice by family physician; opposition from relatives 15 l 7.0 Frightened by rumors 3 f Passed the age of 40 yr. IS Methods changed :m TOTAL 2.',7 It cannot be overemphasized that these low dosage preparations have many obvious advantages if they prove to have 100% contraceptive efficiency. The salient features of our total experience with all the oral contraceptive preparations mentioned are below. Women Cycles Pregnancies Dropouts Related to drug U nrela ted to drug Total no ,483* It % The clinical effectivity can be seen from our results which show that this method is virtually 100% effective. As regards the use-acceptability, the real index for any method is the number of women withdrawing from the medication for any reason related to the method. In our series, there were 47 women who dropped out because of unpleasant side effects or because they were unable to follow instructions or disliked taking daily tablets. There was another group of 257 women who dropped out after completion of one or more cycles for reasons unrelated to the method. It is evident from Table 6 that 217 women gave up this method for valid reasons. Thus, there were only 30 women who changed the method after 9-12 months of medication. This fact points out one more facet of this problem-the effectiveness is not the only consideration in the continuation of a method and each couple assesses the merits and demerits of the method they are using in terms of their own needs and preference, which may change as time passes. In short, even if we include this group of 30 women under the category of *Total of 806 years. ttotal of 0.12/100 women-years.

7 292 SHAH FERTILITY & STERILITY dropout due to reasons connected with the method, the corrected dropout in our series is 12%. In other words, our data indicate that the oral pill method is acceptable to 88% of our women, irrespective of any level of literacy. It may be of some interest to know that 14 of these 30 women preferred to have the IUD, while the remaining 16 convinced their husbands to use a condom. It is common knowledge that postinsertion bleeding and expulsion, which mar the acceptability and efficiency of a good method like IUD, are the 2 most troublesome problems associated with IUD. To the present time, various forms of treatment have been tried in the case of bleeding but none has proved entirely satisfactory and the general feeling is that unless we learn more about the bleeding mechanism, it can not be prevented or minimized. With a hope to minimize the unnecessary bleeding after insertion of IUD, we thought it would be useful to determine whether these women who utilized oral contraception for several months would have the aforementioned side reactions in the same frequency. Although our data are based on a small series, it is still worth reporting. We studied 14 women who were maintained on oral medication for a year or more prior to IUD insertion; 7 of the 14 remained on the pills for 2 cycles after insertion. Thus, there were 3 groups where IUD was inserted: (1) control, (2) those who had preinsertion oral treatment, and (3) those who had preinsertion oral as well as postinsertion oral medication for 2 cycles. Our preliminary results indicate that pre- and postinsertion oral treatment does not appear to minimize the frequency of bleeding or expulsion (Table 7). However, these findings are based on a small number of subjects and since this work is being continued, they are open to revision at a later date. TABLE 7. Effect of Oral Therapy Used with IUD Reactions Cycle 1 Spotting to severe bleeding (week 1 only) Broken or continuous bleeding Menorrhagia Menorrhagia excluding Cycle 1 Expulsion * Total, 80 subjects. t Total, 7 subjects. t Total, 7 subjects; 2 cy{']cs. In Cycle 3. Control* Oral therapy Preinsertiont Pre- & postinsertiont

8 VOL. 19, No.2, 1968 ORAL PROGESTOGENS 293 SUMMARY The preference of the various methods by "cafeteria" approach in 200 consecutive married subjects attending a family planning clinic is discussed. The clinical experience encompassing treatment of 636 Indian women (belonging to a low socioeconomic level) for 10,483 cycles illustrates that, irrespective of lower educational status, the oral pill method is highly efficient and acceptable to young Indian women. The preliminary data on the sequential 10/10 schedule suggest that this small dose is virtually 100% effective for oral contraception in Indian women. Pretreatment with the contraceptive pill or administration of the pill for 2 cycles following IUD insertion does not protect women from untoward side reactions, i.e.. bleeding or expulsion. Department of Endocrinology Indian Cancer Research Center Parel, Bombay 12. India REFERENCES 1. BEHRMAN, S. J. Proceedings of the Symposium on Agents Affecting Fertility, Austin, C. R., and Perry, J. S., Eds. Biological Council, Churchill, London, 1965, p MEARS, E. Proceedings of the Symposium on Agents Affecting Fertility, Austin, C. R., and Perry, J. S., Eds. Biological Council, Churchill, London, 1965, p ISRAEL, S. Contraceptive testing in India. Population Rev 10:51, SHAH, P. N. Proceedings of the Seminar on Modern Contraceptive Devices, Purandare, B. N., Ed. Bombay, SHAH, P. N. Low dosage oral ethynodiol diacetate tablets for long term contraception in Indian women. Brit Med J 2:1431, CHANDRASEKHARAN, C. Fertility Trends and National Policy Proceedings of the Fifth All India Conference in Family Planning, Patna, 1964, p SHAH, P. N. Proceedings of the Third Asia & Oceania Congress of Endocrinology, Litonjua, A. D., Ed., Manila, 1967.