Clomiphene citrate & dexamethazone in treatment of clomiphene citrate resistant PCOS

1. A Elnashar, E abdelmageed, M Fayed, M Sharaf
Benha University Hospital, Egypt
Aboubakr Elnashar

2. C C is the traditional first-line treatment for
chronic anovulation that characterizes PCOS
(Lidor et al, 2000).
However, 25% of PCOS women fail to ovulate
with incremental doses of CC. In addition, clinical
data revealed a discrepancy between ovulation
rates (75%) and conception rates (35%) during
CC treatment (Yen, 1991).
Aboubakr Elnashar

3. The use of corticosteroid for the treatment of
ovulatory dysfunction was first reported in 1953
by Jones et al & Greenblatt (Azziz et al, 1999).
Parsanenzhad et al, (2002) had reported the
novel use of the Dexa (high dose, short course)
for inducing ovulation in anovulatory women with
PCOS & normal DHEAS.
Dexa therapy during the follicular phase has been
described without any side effects or serious
sequelae (Edwards et al, 1996).
Aboubakr Elnashar

4. Objective
was to evaluate the efficacy of adding Dexa (high
dose, short course) to CC in CC- resistant PCOS
with normal DHEAS.
Aboubakr Elnashar

5. Patients and Methods
Sample size was calculated
80 infertile women with CC- resistant PCOS were included.
Our inclusion criteria:
1- Age: between 18-39 years.
2- Period of infertility > 2 years.
3- Serum DHEAS within normal levels (80-400 ug/dl).
4- No treatment was taken during the last 2 months prior to
the Dexa treatment.
Aboubakr Elnashar

6. Patients were randomly assigned into 2
groups.
Group I (40 women): CC 100 mg/d from D3 to 7
of the cycle combined with Dexa 2 mg /d, in two
divided doses, from D 3 to 12 of the cycle.
Group II(40 women): Same protocol of CC
combined with placebo.
HCG (10.000 U) was given when at least one
follicle measured 18 mm & timed intercourse was
advised.
Aboubakr Elnashar

7. Outcome Measures
The primary outcome was the ovulation rate in the treatment
cycle.
Secondary outcomes included number of follicles of >18
mm, endometrial thickness & pregnancy rate.
Aboubakr Elnashar

8. Results
•Dexa was very well tolerated as no patients
complained of any side effect.
Aboubakr Elnashar

9. Baseline features & clinical outcomes of the two treatment groups
P valueGroup II
(n=40)
Group I
(n=40)Variable
0.0525.1502.378323.3803.5941Age (Y)
>0.053.17101.38962.11000.9882Duration of infertility (Y)
>0.0529.5955.795829.3815.1195Body mass index (Kg/m2)
>0.050.96270.08510.89480.0940Waist /Hip ratio
0.05
0.05
32 (80%)
8 (20%)
31 (77.5%)
9 (22.5%)
Menstrual pattern:
Oligomenorrhea or Amenorrhea
Eumenorrhea
0.05(13) 32.5%(11) 27.5%Hirsutism
0.05107.7885.1593.3781.52DHEA-S (ug/dl)
0.057.03000.74098.82001.4906Endometrial thickness (mm)
0.0512.500.7112.501.61Day of HCG administration
<0.050.15±0.041.25±0.67Follicles >18 mm
<0.001(6) 15%(30) 75%Ovulation rate
<0.05(2) 5%(16) 40%Pregnancy
Aboubakr Elnashar

10. Characteristics of both Dexa responders and non-responders
SignificanceNon-
responders
(n=10)
Responders
(n=30)Variable
NS (a)25.22.423.43.6Age of patients (Ys)
NS (a)3.21.392.10.98Duration of infertility (y)
NS (a)29.65.829.45.1BMI (kgm/m2)
NS (a)0.960.090.890.09W/H ratio
S (b)6 (60.0%)25 (83.3%)Oligomenorrhea or
Amenorrhea (n=31)
S (b)4 (40.0%)7 (23.3%)Hirsutism (n=11)
S= significant NS= not significant (a) t test (b) X2 test
•Responders were more often amenorrheic than non-responders.
•About hirsutism, the population sample (n=11) was too small to allow statistical
analysis. Aboubakr Elnashar

11. Discussion
•Several mechanisms have been proposed
Ovarian function:
•Dexa acts directly on the pituitary gland to suppress the
action of E2, which may be involved in the process of induction of ovulation by Dexa-CC treatment
(Terkawa,1985).
•Dexa lowers hypothalamo-pituitary LH secretion (Suter & Schwartz,
1985; Saketos et al 1993)
•Dexa acts indirectly by increasing GH (Casaneuva et aL, 1990), serum
IGF-1 (Miell et aL, 1993) & consequently follicular fluid IGF-1.
•Dexa suppress adrenal androgen production (T & DHEAS)
(Haning et al, 1985) and therefore reduce circulating androgen levels in hyperandrogenic women (Karpas
et al, 1984; Ho Yuen & Mincey, 1983).
Aboubakr Elnashar

12. •Reducing ovarian androgen production while
suppressing circulating DHEAS as a prehormone for ovarian
steroidogenesis (Haning et al, 1985) presumably lowers elevated intrafollicular androgen
levels, which appear to impair folliculogenesis.
•Dexa may directly enhance follicular
development (Smith et aL, 2000).
•Dexa may enhance the FSH-stimulated follicular
progesterone production (Roy et al, 2003).
The endometrial thickness:
The adverse endometrial effect seen with CC, are
not seen with Dexa. The endometrium was of
adequate thickness to allow implantation.
Aboubakr Elnashar

13. •High dose, short course Vs Low dose, long
course of Dexa (0.5 mg/day for one month) (Diamant
& Evron, 1981; Lobo 1982; Daly 1984; Hoffman, et al., 1985; Trott, et al., 1996; Isaacs, 1997).
Low dose, long course:
Favourable endometrial effect is unlikely (Polak de Fried
et al, 1993)
Ovulation rates: 55% to 80%
Pregnancy rates: 8.3% to 49%.
•The high dose, short course regimen:
higher ovulation & pregnancy rates &
more convenient to the patient.
•Although the high dose, short course is more
appropriate, further studies comparing the two
regimen are required (Beck et al, 2005, Systematic review of the Cochrane
library ).
Aboubakr Elnashar

14. Conclusion
1. Induction of ovulation by adding Dexa (high
dose, short course) to CC in CC- resistant
PCOS with normal DHEAS is associated with:
no adverse antiestrogenic effect on the
endometrium
ovulation and pregnancy rates in a significant
number of patients.
2. It is an effective, inexpensive & safe method &
may be tried before gonadotropins or
laparoscopic ovarian drilling.Aboubakr Elnashar

15. Thank YouAboubakr Elnashar
Aboubakr Elnashar