many years, the standard method of Emergency Contraception was the Yuzpe regimen1.
While it is a reasonably effective regimen, it is associated with a high incidence
of nausea and vomiting, mainly due to the oestrogen component of the pills. To
avoid these side-effects, a number of studies have been conducted to assess the
value of levonorgestrel alone for Emergency Contraception.
Levonorgestrel is a potent progestogen which is orally active. When 0.75mg of
levonorgestrel is administered by mouth, the peak plasma level is achieved within
1.9 hours, with a peak plasma concentration of 9 to 11.5µg/ml. The plasma half-life
is 8.9 to 14.5 hours. The use of levonorgestrel for Emergency Contraception was
first reported by Hoffman2. In this study, a single dose of 0.6mg of levonorgestrel
was administered within 12hours of an unprotected intercourse. The pregnancy rate
The first randomised comparison of
the levonorgestrel with the Yuzpe regimen was carried out in WHO supported study3.
In this study, women requesting emergency contraception within 48 hours of an
unprotected intercourse were randomised to receive either the Yuzpe regimen or
levonorgestrel (0.75mg at the time of presentation and repeated 12 hours later).
Because the results were very encouraging, WHO conducted a multicentre study comparing
the Yuzpe regimen with levonorgestrel4. In this study, women requesting Emergency
Contraception within 72 hours of unprotected intercourse were recruited.
In these two studies, 2878 women were recruited; 1437 were randomised to the Yuzpe
regimen and 1441 were randomised to the levonorgestrel group. The outcome was
available in 1403 in the Yuzpe group and in 1386 in the levonorgestrel group.
1400 women in the Yuzpe group and 1384 women in the levonorgestrel group fully
complied with the regimens. The characteristics of the women are shown in Table
1. It can be seen that they are similar in the two groups of women.
Table 1 : Characteristics of women in the Yuzpe
and levonorgestrel groups
age (yr) ||27.0||27.2|
cycle length (days)||29.3||29.5|
body mass index (Kg/m2) ||21.6||21.6|
of women with previous pregnancies
between coitus & treatment
| || |
|25 - 48 h||37.5%
- 72 h ||10.7% ||13.5%|
between coitus and estimated day of ovulation
| || |
1 day before||42.9%||45.9%|
1 day after||29.1% ||31.1%|
| || || |
pregnancy rates and efficacy of the two groups are shown in Table 2. The pregnancy
rate in the Yuzpe group was significantly higher than that in the levonorgestrel
group. Using the pooled estimates of the fecundity of women at various parts of
the menstrual cycle5, we estimated the number of expected pregnancies in the two
groups of women if no treatment was given. This was compared to the number of
observed pregnancies in the two groups of women and the percentage of pregnancies
prevented was calculated as the efficacy of the two methods. It can be seen that
the efficacy of the levonorgestrel regimen was significantly higher than that
of the Yuzpe regimen.
2 : The pregnancy rates and estimated efficacy in the Yuzpe and levonorgestrel
(95% confidence intervals)
= p < 0.01; b = p < 0.005|
The incidence of side-effects of the two regimens
are shown in Table 3. It can be seen that the incidence of nausea, vomiting, dizziness
and fatigue in the Yuzpe group was significantly higher than that in the levonorgestrel
3 : Incidence of side-effects
| || |
p<0.05|| || |
An important finding from these two studies is the reduction in efficacy of the
method with increase in the coitus-treatment interval. The implication is that
the drugs must be given as early as possible after an unprotected intercourse
in order to achieve maximal efficacy. Barriers to the easy access to Emergency
Contraception must be removed so that the methods can be used effectively. Another
important factor affecting the pregnancy rate is the occurrence of further acts
of intercourse. The results showed that in women who had further acts of intercourse
after the administration of Emergency Contraception, the pregnancy rates were
higher. Therefore the women should be counselled that the emergency contraception
cannot protect the women against pregnancy if they had further acts of intercourse
subsequent to the use of Emergency Contraception.
The mechanism of action of levonorgestrel in emergency contraception is not yet
known. In a study by landgren et al6 volunteers were given four to five doses
of 0.75 mg of levonorgestrel every 48 hours in different parts of the menstrual
cycle. The results showed that if the levonorgestrel was given on day 2, 4, 6
and 8, there was an increase in the duration of the follicular phase. When the
levonorgestrel was given from day 9 onwards, there were varying effects on the
menstrual cycle including anovulation, deficient luteal function and no effect.
There were also variable effects on the endometrium. In another study7 it was
found that 0.4 mg of levonorgestrel given 3 to 10 hours post-coital could lead
to a reduction in the number of sperms in the uterine cavity beginning from 3
hours after treatment. There was pronounced alkalinization of the intra-uterine
fluid beginning at 5 hours after treatment. There was also an increase in viscosity
of cervical mucus. However, since the regimens used in these studies were different
from that used in the two clinical studies, it is not certain whether these results
can be extrapolated to the regimen used in the clinical studies. We have recently
studied the effects of levonorgestrel on the in-vitro sperm function and
found that levonorgestrel has only minimal effects on the sperm function.
Despite its efficacy, it must be emphasized that levonorgestrel should not be
used as a regular post-coital contraceptive. In a multicentre study conducted
by WHO8, levonorgestrel was tested for its efficacy as a regular post-coital
contraceptive. In this study, the women were given 0.75 mg of levonorgestrel within
8 hours of intercourse followed by another dose 24 hours later. Further doses
were given after each further act. There were two pregnancies from 259 cycles.
Although the pregnancy rate was only 0.8% per cycle, the pearl index was 10. Moreover,
over 20% of the women had some form of menstrual disturbance. Therefore, women
who are expected to have regular sexual intercourse should be advised not to rely
solely on post-coital levonorgestrel as the method of contraception. Other
more reliable methods of regular contraception should be discussed.
Levonorgestrel was more effective and better tolerated than the Yuzpe regimen
in emergency contraception. The efficacy decreases with increase in coitus-treatment