Volume 200, Issue 5 , Pages e27-e29, May 2009
Evaluation of mifepristone as a once a month contraceptive pill
Article Outline
Objective
The purpose of this study was to assess the efficacy and safety of mifepristone as a contraceptive pill.
Study Design
A prospective case-control study was conducted in a tertiary care center of North India. The study group (n = 86) was given 200-mg mifepristone tablets on the 16th day of the menstrual cycle. The control group (n = 92) received combined oral contraceptive (COC) as per protocol. Subjects were followed for drug compliance, satisfaction, side effects, and failure.
Results
Acceptability of mifepristone was significantly higher in educated population (P < .001), with fewer side effects (P = .001), good satisfaction (P < .001), and higher compliance rate (P = .05). The oral contraceptive pill group had higher adverse biochemical parameters.
Conclusion
Mifepristone can be used as a monthly contraceptive pill effectively.
Key words: contraceptive pill, mifepristone, monthly
Throughout history, mankind has tried to limit family size by various natural and artificial means. Luteal phase contraceptive is a new and promising concept. Mifepristone, an antiprogesterone agent, has multiple potential antifertility actions.
It acts by delaying or inhibiting ovulation in preovulatory phase. In the luteal phase, it acts by its antiprogestational activity, thereby inhibiting formation of secretory endometrium and implantation of the embryo. Researchers have evaluated its use as an early luteal phase contraceptive with a good contraceptive efficacy. In all these studies, women had to have their urine tested for luteinizing hormone (LH) surge for timing of drug administration.
The present study was planned to evaluate the efficacy and utility of mifepristone as a once-a-month mid-cycle contraceptive in women with regular cycles, without testing for the LH surge.
Materials and Methods
A prospective case-control study was conducted in a tertiary care center of North India to evaluate the use of mifepristone as once-a-month oral contraceptive with ethical clearance from the institutional ethical committee. Subjects, aged 20-35 years, with regular menstrual cycle for oral contraception, were recruited from the outpatient clinic of the Department of Obstetrics and Gynecology after taking informed consent.
Subjects having a chronic illness with or without drugs (diabetes, hypertension, tuberculosis, jaundice, heart disease, epilepsy), on erythromycin or antifungal ketoconazole, with a bad obstetric history or menstrual irregularities, previous ectopic pregnancy, adnexal mass, severe anemia, inherited porphyria, adrenal failure, allergies to mifepristone, and lactating mothers were excluded.
Subjects were divided into study and control groups. The division was on the basis of the woman's choice and willingness to try a new drug. The study group was given 200-mg mifepristone tablets orally once a month on day 16 of a regular menstrual cycle of 28-30 days. Women not ready for termination of pregnancy in case of contraceptive failure were excluded.
Control group included age-matched healthy females who chose combined oral contraceptive (COC) pills after counseling. COC contained 35 μg ethinyl estradiol and 0.5 mg norgestrel. One pack had 21 hormonal pills and 7 inert pills. Subjects were instructed to take 1 pill daily throughout the month.
All subjects were followed monthly for compliance, satisfaction, side effects, and failure. Satisfaction was evaluated on a visual analog scale, taking 7-10 as good satisfaction, 4-6 as moderate satisfaction, and ≤ 3 as poor satisfaction. Biochemical tests for hemoglobin, liver function tests, and lipid profile were performed at registration and repeated 3 monthly.
The data collected were subjected to statistical analysis using SPSS version 13.0 (SPSS, Inc, Chicago, IL). The proportions of categorical data were compared using Pearson's χ2 test. Comparison of parametric data in 2 groups was done using Student t test, and for comparison within a group at 2 different time intervals, paired t test was used.
Results
A total of 80 cases (444 cycles with longest follow-up of 12 months and shortest follow-up of 2 months) and 83 controls (504 cycles with longest follow-up of 12 months and shortest follow-up of 2 months) were studied. Age and parity were comparable in both groups but more urban educated women tried the new drug (Table 1).
TABLE 1. Demographic characteristics of subjects
| Area of residence | Education | |||
|---|---|---|---|---|
| Rural | Urban | < Class 8 | > Class 8 | |
| Study group (n = 86) | 20 (23.3%) | 66(76.7%) | 13(15.1%) | 73(84.9%) |
| Control group (n = 92) | 35(38.0%) | 57(61.9%) | 32(34.8%) | 60(65.2%) |
| P = .033 | P = .002 | |||
Side effects were significantly less in the study group (P = .001). Intermenstrual bleeding (12.5%) and prolonged cycles (5%) were the only side effects among the study group (Table 2). Satisfaction level was higher in the study vs the control group (P < .001; Table 3).
TABLE 2. Occurrence of side effects in both groups
| Study group (n = 80) | Control group (n = 83) | P value | |
|---|---|---|---|
| No side effect | 66(82.5%) | 43(51.81%) | <.001 |
| Side effects | 14(17.5%) | 40(48.19%) | |
| Intermenstrual bleeding | 10(71.43%) | – | |
| Prolonged cycles | 4(28.57%) | – | |
| Weight gain | – | 16(40.0%) | |
| Gastritis | – | 13(32.5%) | |
| Breast heaviness | – | 4(10.0%) | |
| Headache | – | 3(7.5%) | |
| Candidiasis | – | 2(5.0%) | |
| BTB | – | 2(5.0%) |
TABLE 3. Satisfaction level in the study and control groups
| Satisfaction level | Study group (n = 80) | Control group (n = 83) | χ2 | P value |
|---|---|---|---|---|
| No. | No. | |||
| Good | 42(52.5%) | 39(46.99.0%) | 0.4950 | .48166 |
| Fair | 35(43.75%) | 20(24.1%) | 7.038 | .007 |
| Poor | 3(3.75%) | 24(28.92%) | 18.6667 | <.001 |
In the study and control groups, respectively, 21.25% and 39.94% of subjects opted out. The reasons for discontinuing the drug in the study group were fear of a new drug (47.2%), side effects (35.2%), and desire to conceive (17.6%). The majority of the control group left COC because of forgetfulness (48.27%), side effects (44.82%), and desire to conceive (6.91%).
Compliance in the study group was 78.75% vs 65.06% in the control group (P = .05). Out of 3 subjects who left the study group for desire to conceive, 2 (66.67%) conceived within 3 cycles. There were 5 failures (all user failure) in the control group (Pearl index = 11.65) vs 1 in the study group (Pearl index = 2.7) (P = .026). There was no prolongation of cycle in this subject, who conceived while on mifepristone.
Biochemical parameters showed an increase in hemoglobin in both groups, but increases in serum alkaline phosphatase and serum glutamyl pyruvate transaminase (SGPT) in the control group only (P = .005 and .042, respectively). Serum cholesterol and triglycerides increased significantly in the control group (P value = .045 and < .001, respectively). No significant change in serum low density and high density lipoproteins was observed in study group.
Comment
The age of childbearing is increasing, as is the need for more effective and easier contraceptive methods. Hence, evaluation of mifepristone as a once-a-month contraceptive pill was found to be safe, independent of coitus, easy to use, with reasonably good contraceptive efficacy.
In the study group, 12.5% mifepristone subjects witnessed a mid-cycle bleed, followed by normal menstruation. There was no failure in the women experiencing this mid-cycle bleed.
Swahn et al1 reported 13.04%, Hapangama et al2 15%, and Gemzell-Danielsson et al3 35% incidence rates of intermenstrual bleeding in their studies, respectively.
Failure rate of COCs was higher (11.65 per 100 women years) than reported in literature (0.2-0.3 per 100 women years with perfect use,4 and 8 per 100 women years for typical use), probably due to the women in this group being illiterate and of a rural background, thereby not realizing the importance of regular pill intake.
There was 1 failure out of 444 treatment cycles in the mifepristone group in the present study. Hapangama et al2 reported 2 failures out of 178 cycles; 1 was true treatment failure and other did not receive mifepristone due to nondetection of LH surge. Gemzell-Danielsson et al3 reported 1 failure out of 169 treatment cycles.
Of the 3 subjects who discontinued mifepristone because they wished to conceive, 2 (66.67%) conceived within 3 cycles, indicating an early return of fertility. Ovulation is expected within 1-2 weeks of discontinuing COCs, although the 1974 Royal College of General Practitioners study suggested a slight but transient decline in fertility.5
The present study, in agreement with Brown et al,6 showed that mifepristone can act as an effective monthly contraceptive pill, given on a fixed day in the mid-cycle without detecting LH surge in subjects having regular cycles.
Acknowledgement
We thank the Indian Council of Medical Research for providing financial assistance for the project.
References
- . The effect of RU486 administered during the early luteal phase on bleeding pattern (Hormonal Parameters and Endometrium). Hum Reprod. 1990;5:402–408
- . Feasibility of administering mifepristone as once a month contraceptive pill. Hum Reprod. 2001;16:1145–1150
- . Early luteal phase treatment with mifepristone (RU486) for fertility regulation. http://humrep.oxfordjournals.org/cgi/content/abstract/8/6/870Accessed June 30, 2008
- . Berek and Novak's gynecology. In: 14th ed.. Philadelphia, PA: Lippincott Williams & Wilkins; 2007;p. 267
- . Fertility following hormonal contraception. Contracept Fertil Sex (Paris). 1983;11:903–907
- . A single dose of mifepristone (200 mg) in the immediate preovulatory phase offers contraceptive potential without cycle disruption. Contraception. 2003;68:203–209
PII: S0002-9378(08)01042-9
doi:10.1016/j.ajog.2008.09.005
© 2009 Mosby, Inc. All rights reserved.
Volume 200, Issue 5 , Pages e27-e29, May 2009
