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ORIGINAL ARTICLE

Effect of mifepristone (25 mg) in treatment of uterine

myoma in perimenopausal woman
Shikha Seth, Neeru Goel, Ekta Singh, A. S. Mathur1, Garima Gupta
Departments of Obstetrics and Gynaecology and 1Radiodiagnosis, Rural Institute of Medical Sciences and Research, Saifai,
District- Etawah, Uttar Pradesh, India

A B S TR A C T

Objectives: To evaluate the effect of Mifepristone (25 mg) on symptomatic myoma in perimenopausal
women.
Study Design: Open label clinical trial.
Materials and Methods: Ninety three perimenopausal women of age 35-50 years having symptomatic
myoma were selected from Gynecology OPD and given 25 mg Mifepristone once daily continuously for three
months. Variables as; baseline uterine size, uterine volume, myoma size, volume, their number, position,
characteristics, hemoglobin and blood parameters, were taken and followed monthly for six months. Bleeding
and pain scores were checked on monthly visits. Changes in above parameters were tabulated during the
first three months treatment phase and then next three post-treatment phase for analysis.
Statistical Analysis: Was done by calculating mean, standard deviation, standard error and percentage
distribution of variables.
Results: Menorrhagia was the most common symptom which led patients to report to hospital. Mean uterine
volume reduced to 63.69% of baseline, Mean dominant Myoma volume reduced to 53.62% and hemoglobin
level raised to 137% after complete three months of treatment. Changes persisted in next three months post-
treatment follow-up, while hysterectomy was required in 10 (12.2%) cases.
Conclusion: Three months treatment of 25 mg Mifepristone effectively controls bleeding, reduces the uterine
and myoma volume and thus can avoid blood transfusion and hysterectomy in a lot of symptomatic myoma
cases.

Key Words: Anti-progesterone, medical treatment, mifepristone, myoma

INTRODUCTION medical management

antagonists, options
selective estrogen are GnRH
receptor agonist
modulators and
(SERM),
aromatase
and inhibitors,
progesterone danazol,
receptor gestrinone,
modulators anti-progestogens
(SPRMS) etc., None
of the drug
myoma yet.has beenterm
Long approved
GnRHby FDA for thetreatment
agonist treatment of is
Leiomyoma
occurring in upis to
the20%
common benign tumor of uterus problematic because of high cost and significant side
between
and lump 35-45
in years ofof
abdomen. age
[1]
women
Severity
withtomaximum
leading of symptoms
incidence
menorrhagia, pain
typically effects
it. due to
Mifepristone hypo-estrogenic
is a environment
synthetic steroid produced
with by
both
depends
They on size,one
represent number
of the of most
myomas, and tumor
frequent location.
indications of anti-progesterone
of the studyonwas andtoanti-glucocorticoid
evaluate activities.
the volume,
effect of The
25 aim
mg
operative
Leiomyomasprocedures
are the mostincited
woman of reproductive
indication for more than age. Mifepristone
and symptomatic uterine and myoma
improvement in view hemoglobin
of avoiding
600,000
annually, hysterectomies
which burden, that
is associated are performed
with to
morbidity, in the US
mortality and hysterectomies and blood transfusions in perimenopausal
huge economic estimated be approximately
$34.4 billion/year.[2]

Other treatment modes for uterine myoma includes -

Myolysis,
current embolization of feeding arteries (invasive), while
Access this article online
Address for Correspondence: Dr. Shikha Seth, Quick Response Code:
Department of Obstetrics and Gynaecology, Type IV, B- Website:
201, Doctors Residence, U.P. RIMS and R Saifai, Etawah,
www.jmidlifehealth.org
Uttar Pradesh - 206 301, India.
E-mail: drseth_shikha@yahoo.com
DOI:
10.4103/0976-7800.109630

22 Journal of Mid-life Health Jan-Mar 2013 Vol 4 Issue

1
 Seth, et al.: Mifepristone in treatment of uterine myoma

women.
speedy In the present study, we had tried the 25 mg dose for
months.symptomatic improvement over a short period of 3
MATERIALS AND METHODS

This open label

Gynecology atyearsclinical
U.P. RIMS trialand
wasRdone at Etawah
departmentoverofaa
period of 2that
hypothesis the from
25 mg 2010Saifai,
JulyMifepristone
to 2012.daily Taking
for three
months
from will offer
the baseline, at least 20%
with 90% power reduction to in myoma
detect volume
the real
difference
82. and 5%
Non pregnant significance sample
womensymptomaticsize calculated
of 35-50 years was
age
(peri-menopausal)
(single or multiple group,
diagnosed having by pelvic myomas
ultrasonography)
who
study.wished to
Excessive conserve their
uterine periods uterus were
bleedinglasting enrolled
was forevidenced for the
passage
days or of clots,
cycles repetitive
length less than 21 days leading more
to thanby8
anemia.
Hemoglobin
30% was less than 11 gm% and hematocrit less than
taken as =criteria for anemia. (Mild = 11-107 gm%gm%,
moderate
decompensated
their written
10-7if gm%,
informed than 4 =gm%).
severe
less consent less than
prior Allinclusion
to women and
gave
and
accepted
woman the
received follow-up protocol of the project. Each
available
gelatin 200 mg the tablet Mifepristone
forby the
chemical 25balance
mg (prepared
and filledfrom in
the 3rd tocapsules)
5th day ofdailymenstrual threefrom
cycle months starting
the hospital. from
Exclusion
10 criteria
cm in history
size, wereofvery
history large myomas
hormonal treatmentgreater
in last than
two
months,
malignancy, pelvic ofinflammatory
breast cancer or (PID),
disease other genital
adnexal
mass, pregnancy,
ultrasonography, suspicion
or anysevere of leiomyosarcoma
contra-indication to disorders. on
Mifepristone
itself as hypersensitivity, renal or hepatic
Blood
base samples
line liver were
and collected
renal function for hemoglobin,
tests, bleeding time, blood counts,
clotting time,
along
size andwith a detailed
volume of baseline
uterus, pelvic
number, ultrasound
size, volume toand
know the exact
location of
myomas
then and
fourmeasuredendometrial thickness
weekly ininfollow-up. Three at the start of
largest diameterstreatment and
(A, B and
C) were
axis in all myomas. As two planes
most of in approximately
myomas are spherical perpendicular
or ellipsoidal,
therefore
C. In casevolume
of was calculated
multiple myomas using formula
largest 0.523 A
one (dominant) was used
B
for
for volume
the calculations
uterine volume, and is,
that follow-up.
4/3 W/2Viscosmi
L/2 formula
T/2, was used
where W
is uterine width on transverse section at uterine fundus;
L is uterine
fundus and length on sagittal
T is uterine sectionmeasured
thickness from internal cervical
on sagittal os to
section
between
keep dailythe anterior
records ofa and posterior
bleeding walls.[3] Women
and symptoms were
as pain, asked
pressure to
or
any
every side
visiteffect
on a on
five table
point calendar.
Likert Symptoms
scale (0 = were
no graded
symptoms, 1 at
=
light, 2 = moderate,
3 = severe and 4 = very severe).

After
were three months
followed up drug Mifepristone
similarly for next three was withdrawn
months but cases
in post-treatment
phase. Datastatistical
appropriate were collected,
methods. tabulated and analyzed using
RESULTS

Total
from 93 cases wereO.P.D.
Gynecology enrolledofover
U.P.2 years fromand
R.I.M.S. July
R. 2010 toEtawah.
Saifai, 2012
Eleven women
completed the 3left treatment
months (drop
treatment out rateMean
protocol. -12%)agewhile
was rest 82
38.47
4.9 years.forDemographic
Reasons parameters are shown asin they Table 1.
reported back drop out cannot
to us during be period
the study commented
of 2 years. never
Abnormal
commonest and excessive
reporteduterine bleeding (AUB) was the
heaviness inproblem
lower abdomen inby2277 cases
(26.83%) (93.96%) followed by
Table 1: Demographic parameters
Parameters N=82
Mean age 38.47 years4.9
Median parity 4 (2-7)
Mean BMI 24.12 Kg/M23.81
Mean height 153.24.8 cms
Caste
Hindu 68
Muslim 13
Christian 1
Socio-Economic- Strata (kuppuswami)
Class I 2
Class II 5
Class III 33
Class IV 42
Education
Illiterate 34
Primary 10
10th stand. 29
Graduation 9
Myoma
Subserous 2
Intramural 74
Submucous 5
 Seth, et al.: Mifepristone in treatment of uterine myoma
60 women as some stopped coming to hospital after
and painAmong
hospital. in 18 AUB,(21.95%) forwas
which
54.8%reported they came
menorrhagia, 26.4%to drug was withdrawn. Menstruation was regained in mean
poly-menorrhagia,
Amount of and 12.2%
bleeding was not exactly menometrorrhagia.
found co-related
with
myomas sizepresented
of myoma with in our study.
normal cycles Four
and4-5 (4.8%)
one women
(1.2%) duration of 34.72 (SD 17.48), days. One case persisted
hypomenorrhea.
of Mifepristone Bleeding
and 75 stopped
women within
(92.68%) days
had of with
start
complete
amenorrhoea
not respond during
to drug treatment
and their phase.
myoma Sixvolume
womencontinued
(7.32%) didto with amenorrhoea and only four required hysterectomy for
increase progressively
Dysmenorrhea, pelvicandpain,
had hysterectomy
heaviness was done later.
backache, and recurrence of heavy bleeding episodes [Table 3]. Initial cycles
urinary
treatment.complaints
Symptom improved
scores a
for at lot
pain in first month of
change
two from atin end average four startshowed significant
of changes
treatment to in post treatment phase were slightly heavier in 45% (27/60)
observed liver of treatment.
enzymes Noprofile
or renal significant
of cases. were
women which responded to hemostatic tranexamic acid.
Median
two number
(range: 1-5) andof leiomyomas
it wasvolume at baseline
two (range: 1-4) atsonography
the end ofwas Incidence of hysterectomy was 12.1% (10/82) in the
months.
22.2), Mean
decreased while uterine
mean volume decreased
of dominant to 63.69%
leiomyoma(SD3
to 53.62% (SD 48.5) after three months of study. In two cases pedunculated submucous myoma
complete
well, whiletreatment.
inones Intra-mural
out prolapsed
of five out and subserous
submucous responded
myomas, two
pedunculated
polypectomy and recurrence.
one was non of cervix
- respondermyomaand
and onerequired
had prolapsed into vagina at 2nd and 3rd month respectively,
hysterectomy
decreased to afor Mifepristone volume
Rate of infall
flattened ingreater
later myoma
half
extent
of treatment
compared
volume to uterine
was [Figure
phase steep volume.
initially
1]. and in whom polypectomy solved the problem. Blood
transfusion was given in only five very severely anemic
He mog lobin c ou nt s impro v e d s ig nif ic ant ly
2.8 gram + SD 1.49, from mean 8.9 gram% at start. Base
line endometrial thickness (ET) at start of treatment was
7.6 + 2.8 which progressively increased in all 82 cases
during the treatment phase with mean 51.9% rise over
three months [Table 2]. Only in two cases ET crossed the
20 mm mark, after which endometrial biopsy was done and
simple endometrial hyperplasia was diagnosed in both the
cases. No specific side effect of the drug was noted except
headache (12%) in first month and hot flush (3.65%) in
second month. Liver transaminases (AST, ALT) were found
raised in 26 (31.7%) women but none have crossed double
of the normal value.

Post-treatment follow-up could be completed only in

Figure 1: Uterine and Myoma volume change in treatment phase
Table 2: Clinical outcomes after Mifepristone treatment
Parameters VolumeSE* Mean percentageSE Change
Mean baseline uterine volume (mm ) 3
302124.518245.3 100%
Mean uterine vol. at 1st month 249856.96 82.73%14.1 17.27% fall
Mean uterine vol. at 2nd month 221457.25 73.32%17.6 26.68% fall
Mean 3rd month end uterine volume (mm3) 192424.712289.2 63.69%22.2 36.31% fall
Mean baseline myoma volume (mm3) 143957.817669.9 100%
Mean myoma vol. at 1st month 107680.43 74.8%36.3 25.2% fall
Mean myoma vol. at 2nd month 87353.59 60.68%55.9 39.32% fall
Mean 3rd month end myoma volume (mm3) 77201.914299.3 53.4%48.5 46.38% fall
Mean baseline Hemoglobin 8.92.1 gm% 100%
Mean 3rd month Hb 11.821.26 137% Mean rise 2.8 gm SD1.49
Mean baseline Endo. thickness 7.62 mm2.81 100%
Mean 3rd month end Endometrial thickness 11.57 mm2.38 151.9% 51.9% rise
* SE: Standard error
 Seth, et al.: Mifepristone in treatment of uterine myoma

general condition.(Hb < 5 gm%) cases to improve their

decompensated and antiglucocorticoid properties in dose dependent
manner.
DISCUSSION Clinical
conducted trialsforusing
varying5-50periods
mg doses of Mifepristone
between 3 to 12 months were
but exact et
Eisinger, doseal.,
and
[5] the duration are yet to be determined.
reported fall of 48% in mean uterine
volume
10 mg while amenorrhoea
mifepristone. Anotherin 61% studyonlybyafter 6 months
Kettle et al., of
Fibroid being a tumor of hyper-estrogenic environment, reported
dose, whileamenorrhoea
100 mg led in
to 40-70%
100% over one
amenorrhoea. year
[6] at 5-10 mg
AUB is the
therefore
GnRH medical
agonists treatment
(Lupride) that
and lowers estrogen
antagonists levels as main reason ofefficiency
worry in women as it affects theirmostly
daily
D a n a
aromatasezo l, G e s t
activity r i n o n e ,
(Letrozole) C a b eorr g o l i n
modifiese , (Cetrorelix),
r eestrogen
duc e s routines,
opt for work
developing hysterectomy
countries.
and
as health
With one
higher
status,
time therefore
management
doses speedy in
and
response
size of (SERM-Raloxifene)
fibroid and improve are effective
symptoms in in reducing
most of the
cases. [4] better
general control
condition of ofbleeding
women isand
achieved,
hemoglobinthis levels,
improves the
relieves
Current studiesdependent
progesterone support that alsogrowth
and of myomaantiprogestins
therefore in humans is anxiety andofprovides
affectivity treatment women a sensehotofflushes
but produce well being
and and
other
(Mifepristone)
modulators and selective progesterone
(SPRMs-Asoprisnil) can besize, receptor
effective in anti-glucocorticoid
comparative study of side-effects.
5 mg, 25 Murphy
mg and 50 et
mg al. [7]
dosage had anda
treatment.
hemoglobin Hormonal
by controlling treatment reduces
bleeding and renders improves
surgery suggested
clinically 25 mg to decrease
significant be the most in effective dose
leiomyoma to cause
volume. We
unnecessary
fibroid as
being a hormonepatient reaches
depended menopause,
tumor because
stops to grow chose 25 mg daily to achieve rapid symptomatic
after menopause. Mifepristone has both antiprogesterone
Table 3: Post treatment follow-up (n = 60)
Parameters for follow-up No. of cases Percentage improvement
rate) in short (improved
side effects. period ofcompliance with low
time (3 months) withdrop out
minimal
Menstruation regained
Within one month 22 36.6
After one month 37 61.6
Bleeding Mechanism of reduced bleeding and myoma size is likely
Amenorrhoea persisted 1 1.6 to be due to structural, functional and micro vascular
Normal cycles regained 32 53.33 effects of Mifepristone on the endometrium and uterine
Heavy required tranexamic acid 27 45 musculature in dose and duration dependent manner. In
Operative treatment study 25 mg Mifepristone reduced uterine size to 63.69%
Polypectomy 2 3.3 of baseline (36.4% decline) while Bagaria et al.,[8] had
Recurrent bleeding requiring 4 6.6 26.6% reduction with 10 mg over 3 months, and Eisinger
hysterectomy
et al., 11% with ultra low 2.5 mg over 6 months [Table 4].[9]

Table 4: Dose duration dependence of Mifepristone by past studies

Authors Dose of Duration of Reduction in uterine volume Endometrial hyperplasia Amenorrhoea at 30 days
mifepristone treatment (%) (+%) (%)
(months)
Bagaria, et al.[8] 10 mg 3 26.6 63.2 84.2
Eisiniger, et al.[5] 10 mg 12 49 13.9 61
5 mg 12 52 -
Fiscella, et al.[14] 10 mg 6 53 4.8
5 mg 6 47 -
Engman, et al.[10] 50 mg 3 28
Eisiniger, et al.[8] 2.5 mg 12 11 -
26% drop out
Carbonell Esteve, et al.[13] 2.5 mg 3 9.6 38.2 46.7
5 mg 3 24.3 35.5 83.1
Present study 2012 25 mg 3 36.4 51.9 92.6
82 cases
 Seth, et al.: Mifepristone in treatment of uterine myoma

Mean myoma volume reduced by 46% with 25 mg dose in hemoglobin

that levels and generalforcondition.
25 mg Mifepristone Studyis supports
our study
Engman
et al., 49%
which
[6] et al.,
[10]is quiet better than other studies as,
decline 28%
withdecline
mgwith
100 in 50 mg
in three and More
months. Kettle in alleviating hysterectomydaily
in 87.8%three
women.months effective
number
rest of of receptors
normal is there
myometrium leiomyoma
therefore more compared
steady fall to
is
seen in volume
uterine it. Submucosal
decreased myomas prolapsed
and simple through cervix
polypectomy servedas REFERENCES
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How to cite this article: Seth S, Goel N, Singh E, Mathur AS, Gupta
G. Effect of mifepristone (25 mg) in treatment of uterine myoma in
perimenopausal woman. J Mid-life Health 2013;4:22-6.
Source of Support: Nil, Conflict of Interest: None declared.