Clomiphene citrate & dexamethazone in treatment of clomiphene citrate resistant PCOS


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Clomiphene citrate & dexamethazone
in treatment of clomiphene citrate resistant PCOS

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Clomiphene citrate & dexamethazone in treatment of clomiphene citrate resistant PCOS

  1. 1. A Elnashar, E abdelmageed, M Fayed, M Sharaf Benha University Hospital, Egypt Aboubakr Elnashar
  2. 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. 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. 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. 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. 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. 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. 8. Results •Dexa was very well tolerated as no patients complained of any side effect. Aboubakr Elnashar
  9. 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. 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. 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. 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. 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. 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. 15. Thank YouAboubakr Elnashar Aboubakr Elnashar