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|Year : 1976 | Volume
| Issue : 4 | Page : 176-179
Poor acceptability of "Pill-a-month" contraceptive - High pregnancy and drop-out rates in a small sample
Rama A Vaidya, Shaila Kore, Asha Adatia, Vidya Iyengar, Suhasini Dikshit, Katayun Virkar
Institute for Research in Reproduction (Indian Council of Medical Research), Jehangir Merwanji Street, Parel, Bombay-400012, India
Rama A Vaidya
Institute for Research in Reproduction (Indian Council of Medical Research), Jehangir Merwanji Street, Parel, Bombay-400012
Source of Support: None, Conflict of Interest: None
A combination of long acting oestrogen-ethinyl estradiol-3cyclopentyl ether 2 mg (Quinestrol) and a progestin-norethindrone acetate-3-cyclopentylenol ether 2.5 mg (Quingestanol acetate) was clinically investigated as a "Pill-a-month" contraceptive in 94 Indian women for 529 months of use. Totally 6 pregnancies occurred due to the method failure, the Pearl index being 13.6 per 100 women years (the 95 per cent confidence region per 100 women years has the lower limit of 4.5 and the upper limit of 30). The drug related drop-out was 68% at the end of 2 years' trial (95 per cent conf. dente region for per cent observed rate has the lower limit of 64 and the upper limit of 72 per cent). The high pregnancy rate has been validated by the multicentric Indian data.
|How to cite this article:|
Vaidya RA, Kore S, Adatia A, Iyengar V, Dikshit S, Virkar K. Poor acceptability of "Pill-a-month" contraceptive - High pregnancy and drop-out rates in a small sample. J Postgrad Med 1976;22:176-9
|How to cite this URL:|
Vaidya RA, Kore S, Adatia A, Iyengar V, Dikshit S, Virkar K. Poor acceptability of "Pill-a-month" contraceptive - High pregnancy and drop-out rates in a small sample. J Postgrad Med [serial online] 1976 [cited 2020 Feb 20];22:176-9. Available from: http://www.jpgmonline.com/text.asp?1976/22/4/176/42818
| :: Introduction|| |
The clinical efficacy, tolerability and acceptability of a novel and practical approach of "Pill-a-month" contraceptive was reported with favourable results by several investigators. ,, Tolerability profile was claimed to be comparative with the conventional oral contraceptives.+ Subsequently a world-wide interest resulted in a number of clinical trials. ,, In a report of W.H.O. Scientific group  in 1973, the current status of "Pill-a-month" could not permit definite recommendation due to the limited nature of data. The present report shows unfavourable data in a relatively smaller sample; the extrapolation of the data to the larger experience from multicentric sample of Indian Council of Medical Research validated the early observation.
| :: Material and Methods|| |
From August, 1971 to October 1973, 94 women attending two clinics of the Institute for Research in Reproduction for fertility regulation opted for "Pill-a-month" contraceptive. This Institute is one of the peripheral centres for the Contraceptive Testing Unit of the Indian Council of Medical Research. Women with history of regular menstrual cycles and without the known contraindications to steroid contraceptives were enrolled in the trial. Postpartum and lactating women were excluded from the trial. Total of 94 women used the method for 529 months. Age and parity distribution are shown in [Table 1].
The "pill-a-month" is an oral formulation containing long acting oestrogenquinestrol 2 mg and a progestogen quingestanol acetate 2.5 mg. The first dose of the combination preparation was given on the second day of the menstrual cycle. The second pill was given on the twenty second day of the same cycle. Subsequently the pill was administered on every twenty eighth day from the previous dose not withstanding the time of withdrawal bleeding. Since the incidence of pregnancy has been reported to be higher in the first month of use,  the couple was advised to use local contraceptive methods (condom, diaphragm, jelly, foam tablets etc.) concurrently for the first month. Prior to the trial, the patients were investigated and examined by physicians for a baseline evaluation of symptoms and physical and pelvic signs. The laboratory investigations to monitor the organ functions and metabolic indices were carried out basally and during the trial. Women attended the clinic for each dose of "pill-a-month". The administration of pill was done in clinics. The follow-up evaluation of bleeding patterns, efficacy, acceptability and side effects was done at each visit. Women were also advised to attend the clinic in the event of any untoward effects.
The probable drug-emergent symptoms were evaluated as baseline data before commencing the therapy and an attempt was made to correlate the side effects with baseline symptoms. This precaution was considered essential to avoid nondrug adverse reactions, fictitiously swelling the incidence of side effects. 
The unfavourable side effects contributed to early high drop out rate which did not permit the fulfillment of the requisite number of 100 women at every ordinal month for life-table methods of analysis. Ninety five per cent confidence range for the accurate value was extrapolated from the observed values of pregnancy and drop-out rates with the help of Hines and Goldzieher's nomograms. 
| :: Results|| |
A total of 529 women months' experience with "pill-a-month" was obtained by the end of the trial. Of the 94 women included in the trial no pregnancy occured in the first month of the drug usage. The observed pregnancy rate by Pearl formula was 13.6 per 100 women years. The lower limit of the true incidence of pregnancy was 4.5 per 100 women years, the value for the upper limit being 30 as derived for 500 cycles from Hines and Goldzieher nomogram for 95 percent confidence range.  In the present trial, the actual number of observed pregnancies when the first 50 women completed 3 cycles each was 3. The computation of probability of no-pregnancies for 3 observed pregnancies is 0.05  This suggests a low protection rate and a drug efficacy of 70% only.
[Table 2] shows the percentage frequency of side effects. Same baseline symptoms continuing during therapy were not considered to be drug emergent side effects. Most common side effects were nausea, vomiting, dizziness, headache and weakness. Thirty one (33.3%) women discontinued from the trial because of these side effects.
Only 21 of 94 women continued using this method of contraception for more than 12 months. Of these 73 women who dropped out by 12 months, 13 did so for either personal reasons or for moving away, 47 had discontinued because of the frequency and severity of associated symptoms, 6 became pregnant due to the method failure. Of 7 women who discontinued because of menstrual disorders, 5 complained of break through bleeding and 2 dropped out because of amenorrhoea. At the end of trial the drug related dropout was 68 per cent (95 per cent confidence region for per cent observed rate has the lower limit of 64 and upper limit of 72 per cent).
| :: Discussion|| |
In the present trial utilizing Hines and Goldzieher's nomograms,  the lower limit of pregnancy rate at 95% confidence range was 4.5. This is close to the observed Pearl Index value of 6.04 derived from the data reported by Mishell and Fried.  The observed pregnancy rate with pill-a-month in the present formulation was 5.1 per 100 women at 12 months in Indian women in multicentric I.C.M.R. trial.  This result is in confirmation with the high pregnancy rate of 7.3 per 100 women at 12 months reported by Mishell and Fried. 
The major determinants of discontinuation were persistent and severe side effects. Thirty three per cent of women dropped out because of the common side effects of hormonal contraceptives. The frequency of these side effects has been computed after exclusion of women who had the same symptoms at the pretherapy evaluation. The incidence of side effects is much higher than the incidence observed in a concurrent trial with the low-dose combination pills, at the same clinics (unpublished data). The mechanism of enhanced adverse reactions with the "pill-a-month" in the present trial is not understood. It may be speculated that the less total body fat in Indian women might contribute to a decreased depot of the steroid-esters and subsequently elevated levels in plasma. This might explain the severe effects.
The high pregnancy rate, the low tolerability and poor acceptability of the pilla-month in Indian population would limit the application for fertility control.
| :: Acknowledgement|| |
We appreciate the continuous support from our Health Educators and Social Workers for this clinical trial. Their sustained efforts at motivation of the women for family planning make these trials a success.
| :: References|| |
|1.||Guiloff, E., Berman, E., Montiglio, Osorlo, R. and Llyods, C. W.: Clinical study of a once-a-month oral contraceptive: Quinestrol-Quingestanol, Fertil. Steril., 21: 110-118, 1970. |
|2.||Hines, D. C. and Goldzieher, J. W.: Clinical investigation: A guide to its evaluation, Am. J. Obst. and Gynec., 105: 450-487, 1969. |
|3.||Larrango, A. and Berman, E.: Clinical study of a once-a-month oral contraceptive: Quinestrol-Quingestanol, Contraception, 1: 137-148, 1970. |
|4.||Lotwin, B. R. and Berman, E.: Once-a-month oral contraceptive: QuinestrolQuingestanol, Obst. & Gynec., 35: 933936, 1970. |
|5.||Lotwin, B. R., Mischler, T. W. and Berman, E.: Further experience with a once a-month contraceptive: QuinestrolQuingestanol, Fertil. Steril., 23: 734-738, 1972. |
|6.||Mishell, D. R. Jr. and Fried, N. D.: Life table analysis of a clinical study of a once-a-month oral steroid contraceptive: Quinestrol-Quingestanol, Contraception, 8: 37-42, 1973. |
|7.||Shah, P. N., Seshadri, Rajeshwari, Rajendra, K. G. and Shah, Urmila: Acceptability, clinical effectivity and laboratory studies in Indian women on "Pill-amonth" oral contraceptive, J. Obst. and Gynec. India, 23: 669-675, 1973. |
|8.||Taber, B. Z., Greanery, M. O. and Bessler, S. A.: Methods for assessing the efficacy of new contraceptive compounds, Pacific Med. Surg., 74: 145-148, 1966. |
|9.||Tejuja, S.: Personal communication. |
|10.||Vaidya, A. B.: Non-drug adverse reaction. In "International aspects of drug evaluation and usage", Ed. A. J. Jouhar and M. F. Graysen, Churchill-Livingstone, London, p. 191, 1973. |
|11.||W.H.O. Technical Report Series No. 527, 1973. |
[Table 1], [Table 2]