Abstract No: 88
TNF-a AND IL-8 PROFILE AFTER DYDROGESTERONE THERAPY ON
DYSFUNCTIONAL UTERINE BLEEDING PATIENTS
W. Adiyono, H. Hardian
Medical Faculty Diponegoro University, Indonesia
Introduction: Dysfunctional uterine bleeding (DUB) is often occur on 75% female at
reproductive age. Human endometrium has unique characteristics, it has very complex
regulation process. Recent studies show that abnormal proliferation of endometrial tissue
is not only regulated by estrogen, but also affected by specific growth factor. The growth
factor and some cytokines may response to ovarium hormon stimulation to regulate
endometrial tissue. It has been reported the angiogenic effect of IL-8 and TNF-a
hyperactivity have an important role in the patophysiology of DUB, The one of DUB
etiology is the increase of blood estradiol level that caused abnormal endometrium
proliferation. The increase of E2 activity will promote dysfunction immune system and also
affect E and P receptors. The activity of IL-1, IL-8 and TNF-a on endometrial tissue will
followed by proliferation of endometrial cell that clinically appear as DUB.
Dydrogesterone is similar to natural progesteron that has not estrogenic, androgenic and
anabolic effect. The one indications of dydrogesterone therapy is menstrual disorder.
This is a preliminary study to determine the efficacy of dydrogesterone administration on
clinical outcome and TNF-a and IL-8 profile on DUB patients.
Material and Methods :
The study were conducted at Anugerah Mother and Child Care Hospital on Semarang,
Central Java, Indonesia on the period August 2001 until April 2002. Twenty six DUB
patients were assigned on the study after signed the informed consent. The diagnosis of
DUB was carried out by Office Hysteroscopy technique. Eighteen patients were assigned
to receive Dydrogesterone and 8 patients receive placebo. The dose of Dydroprogesterone
was 10 mg oral daily, administered for 20 days started at day-5 of menstruation. The
collected data were chief complaint, parity, the result of therapy (stop bleeding or not),
additional treatment needed after first therapy when the bleeding was persist, the level of
TNF-a and IL-8. The level of TNF-a and IL-6 were measured from vein blood sample by
ELISA method. The blood samples were taken at the end of the treatment. The difference
of proportion of chief complaint, parity, cure status and further treatment on 2 groups were
analyzed by c2 test. Non parametrics Mann-Whitney test was employed to examine the
difference of TNF-a and IL-8 between groups. The value of p£ 0.05 is considered as
significant.
Results and Discussion: The data show the age of both groups were similar,
the mean of patients age on Dydrogesterone was 32.2 year (SD=3.64) and 34.1 year
(SD=6.36) on placebo group. The biggest proportion of parity was PII (33.3 % on
Dydrogesterone group and 37.5 % on placebo group). There was no significant different of
parity of both groups (p=0.6). The chief complaint menorrhagia mostly found on
Dydrogesterone group (72.2 %), in the other hand, on placebo group menometrorrhagia was
mostly found (50.0 %). The proportion different was not significant (p=0.2). There is
significant different on the result of therapy, the data show the cure rate on Dydrogesterone
group was 83.3 % compare to 12.5 % on placebo group (p=0.001). Only 3 patients on
Dydrogesterone group need further therapy (1 patients received more addition of
Dydrogesterone and 2 patients need curretage to stop the bleeding), however, on placebo
group 7 patients need further treatments (2 patients received Dydrogesterone and 5 patients
need curretage). The level of TNF-a was significantly (p<0.001) lower on Dydrogesterone
group (124.2 pg/mL; median=66.05 pg/mL) compare to placebo group 685.7 pg/mL
(median=621.2 pg/mL). However, there was no significant different (p=0.2) on IL-8 level
of dydrogesterone group compare to placebo group. The mean level of IL-8 on
Dydrogesterone group was 1176.7 pg/mL (median=1194.4 pg/mL) and 1216.1 pg/mL
(median=1211.4 pg/mL) on placebo group. Since Dydrogesterone has molecular structure
identical to natural progesteron, Dydrogesterone will act as natural progesteron on the
receptor of progesteron that may promote the bleeding to normal mesntrual cycle. Another
possible mechanism is Dydroprogesterone attenuate the activation of cytokine i.e. TNF-a
that may affect angiogenesis by VEGF. Conclusion: Dydrogesterone 10 mg daily for 20
days has efficacy to stop the bleeding on DUB patients compare to placebo.
Dydrogesterone also reduce the level of TNF-a, whereas TNF-a has important rule on
endometrial cell proliferation and angiogenesis on endometrial tissue. Further study is
needed to get more accurate results.
Keywords: dysfunctional uterine bleeding,
dydrogesterone, TNF-a, IL-8, angiogenesis