Role of GnRH agonist in benign gynaecological disorders

1,084 views

Published on

Role of GnRH agonist in benign gynaecological disorders

Published in: Health & Medicine
0 Comments
20 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,084
On SlideShare
0
From Embeds
0
Number of Embeds
5
Actions
Shares
0
Downloads
83
Comments
0
Likes
20
Embeds 0
No embeds

No notes for slide

Role of GnRH agonist in benign gynaecological disorders

  1. 1. Role of GnRH agonist in benign gynaecological disorders Aboubakr Elnashar Benha University Hospital, Egypt ABOUBAKR ELNASHAR
  2. 2. Contents  GnRHa Administration Use in benign gynaecological disorders 1. Endometriosis 2. Uterine fibroids. 3. Thinning agent in DUB (prior to endometrial ablation). 4. Pituitary down-regulation (in long protocol of IVF and induction of ovulation). 5. Adenomyiosis ABOUBAKR ELNASHAR
  3. 3. GNRH AGONISTS Produced by Modification of the native GnRH decapeptide at 6 & 10 positions Glp-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 LHRH Glp-His-Trp-Ser-Tyr-Ser(But)-Leu-Arg-Pro-Azgly-NH2 Goserelin 100 times more potent than natural LHRH ABOUBAKR ELNASHAR
  4. 4. Mechanism: After initial agonistic action (flare response), down-regulation & desensitization of the pituitary: hypogonadotrophic, hypogonadal state. ABOUBAKR ELNASHAR
  5. 5. Effects of GnRha Within 12 h of administration: [flare effect lasting 24-48 h] : 5 fold increase of FSH, 10 fold rise in LH & 4 fold elevation in E2. Continuous administration : opposite effects: internalization of the agonist /receptor complex & decrease in the number of receptors (down-regulation). : paradoxical suppression of the pituitary Gnt synthesis & liberation (desensitization). ABOUBAKR ELNASHAR
  6. 6. The decreased levels of FSH & LH: 1. Arrest of follicular development & 2. Decrease in sex steroid levels to castrate levels. Postmenopausal E2 levels are commonly reached after 21 days. The pituitary blockade persist during agonist treatment but it is reversible after therapy. ABOUBAKR ELNASHAR
  7. 7.  Administration • Goserelin: SC into the anterior abdominal wall every 28 days +/- 2 days {1. Best route of absorption and steady dissolution of depot 2. The trunk area is less sensitive than the thighs: negligible pain on injection} ABOUBAKR ELNASHAR
  8. 8. Indications in benign gynaecological disorders 1. Endometriosis. 2. Uterine fibroids. 3. Thinning agent in DUB (prior to endometrial ablation). 4. Pituitary down-regulation (in long protocol of IVF and induction of ovulation). 5. Adenomyiosis 6. Before & during chemotherapy for breast cancer to preserve ovarian functionABOUBAKR ELNASHAR
  9. 9. 1. Endometriosis  GNRHa: An appropriate therapy of CPP, even in the absence of laparoscopic confirmation of E, provided that a detailed evaluation fails to demonstrate other cause (ACOG Recommendations Grade (B) ABOUBAKR ELNASHAR
  10. 10. Indications GnRHa with HT addback should be considered as 2nd line treatment: No response to CHCs or progestins Recurrence of symptoms after initial improvement (SOGC, 2010) ABOUBAKR ELNASHAR
  11. 11. Types of GnRHa PriceEPcompanyDoseRouteNamePreparation 750 1550 540 Abbot3.75 mg/4w 11.25 mg/12 w 2.8 ml, 1 ml daily IM, SC IM, SC Lupron Lucrin Leuprorelin 500Astrazenica3.6 mgSCZoladexGoserelin 605 266(7syr) FerringCR: 3.75mg, 0.1mg then 0.05 mg IM, SCDecapeptylTriptolerin Sanofi0.5 mg then 0.2 mgNasal, SCsuperfactBuserelin Pfaizer0.2 mg bidnasalSynarelNafarelin ABOUBAKR ELNASHAR
  12. 12. Side effects: GnRHa alone: symptoms of estrogen deficiency hot flushes insomnia Loss of libido, vaginal dryness, emotional instability, depression, headache. loss of BMD, which is not always reversible. ABOUBAKR ELNASHAR
  13. 13. Add-back therapy: Aim: To prevent demineralization of bone & menopausal symptoms. GnRha should not be given as a single agent for >6 ms. GnRHa should not be used for any length of time in the absence of HT addback (SOGC, 2010). ABOUBAKR ELNASHAR
  14. 14. Addbackrationale:There is a threshold serum estrogen concentration that is low enough that endometriosis is not stimulated but high enough that hypoestrogenic symptoms are prevented (Barbieri,1992). This concentration is the same as that achieved with physiologic HT for menopausal women. Addback GnRHa Oestradiol Endometriosis symptoms Menopausal symptoms ABOUBAKR ELNASHAR
  15. 15. •Estrogen-progestagen combination. Tibilone (livial): 2.5 mg/d. Bisphosphonates: Etidronate.  ABOUBAKR ELNASHAR
  16. 16. Efficacy: GnRHa: Pain relief 85-100% persisting for 6-12 months after cessation of tt. (Winkel et al,2005 ) GnRHa Vs other hormonal tt: No difference with respect to pain relief or reduction in E deposits (Cochrane library, 2005). ABOUBAKR ELNASHAR
  17. 17. 2. Uterine fibroids The main benefits  Decrease myoma size by about 38% and 41% after 8 and 12 weeks respectively (hysteroscopic myomectomy* - proper reconstruction of uterine anatomy - decrease postoperative adhesions).  Decrease uterine size by about 32% after 12 weeks(easier surgery). Audebert AJM et al. British Journal of Obstetrics and Gynaecology 1994; 101: Suppl 10, 29–32 Benagiano G et al. Fertility and sterility 1996; 66: 223–229 ABOUBAKR ELNASHAR
  18. 18.  Amenorrhoea and endometrial atrophy:  relief from excessive uterine bleeding.  restoration of normal Hb concentration.  detection of stromal fibroids.  Possibility to schedule operation and avoid emergency.  Decrease fluid absorption during hysterscopy (due to decreased endometrial vascularization) & reduce risk of volume overload.  Significant decrease blood loss during operation. (No need for blood transfusion & easier surgery).  Subjective assessment scores of pain symptoms decreased by 81% after 8 weeks of treatment. ABOUBAKR ELNASHAR
  19. 19.  Symptom relief  Patient feels better after 2nd injection.  Operation can be scheduled to accommodate waiting lists or to suit patient’s personal plans  Improvement of patients’ haematological status before surgery  Reduction of blood loss before and during surgery  Need for fewer transfusions  Reduction in size of the fibroids before surgery9  Simpler and shorter surgery  Reduction in postoperative recovery time  Shorter hospital stay Audebert AJM et al. British Journal of Obstetrics and Gynaecology 1994; 101: Suppl 10, 29–32 Candiani GB et al. Acta Obstet Gynecol Scand. 1990; 69: 413–415 Lumsden MA et al. British Journal of Obstetrics & Gynaecology 1994; 101(5): 438–442ABOUBAKR ELNASHAR
  20. 20. Blood picture & reduced uterine volume in with Fibroids Pre-treatment 3 months % change 6 months % changes Haemoglobin ( g/dl) 7.4 13.2 +78* 13.6 +84** Hematocrit ( %) 26.1 39.8 +52* 40.3 + 55** Serum Iron ( Mc/dl) 21.7 53.8 +14* 60.8 +180 ** TIBC ( Mc/dl) 394 344 -13* 336 - 15** Serum Ferritin ( ng/dl) 9.7 17.2 +77* 31.5 +225*** Uterine Volume (ml) 587 298 -49 288 -51** R.M.Miller et al British journal of Obstetrics and Gynaecology . Feb 1992. Vol 99. Suppl 7. Pp 37-41 *P < 0.01 compared with treatment ** p = NS compared with 3 month of treatment ***p <0.01 compared with 3 month of treatment ABOUBAKR ELNASHAR
  21. 21. Significant reduction fibroids volume ZOLADEX 3,6 mg reduces fibroid volume 50 100 150 200 250 300 Immediate surgery group ZOLADEX group Meanfibroidsize(ml) Audebert AJM et al. British Journal of Obstetrics and Gynaecology 1994; 101: Suppl 10, 29–32 Benagiano G et al. Fertility and sterility 1996; 66: 223–229 ABOUBAKR ELNASHAR
  22. 22. Dose: Two depots of ‘Zoladex’ given with 4 weeks apart, then ablation 0-2 weeks after the 2nd depot. ABOUBAKR ELNASHAR
  23. 23. 5. Adenomyosis: Although adenomyosis & endometriosis are different diseases, both of them grow& regress in an oestrogen-dependent fashion (Kitawaki et al,2006). Adenomyotic tissue contains: 1. Steroid receptors 2. Aromatase& sulphatase enzymes. Circulating &locally produced oestrogens stimulate the growth of tissue mediated by the oestrogen receptors. ABOUBAKR ELNASHAR
  24. 24. To date, there is no agreement on the most appropriate therapeutic methods for managing women with uterine adenomyosis who want to preserve their fertility (Wang et al, 2009). Hormonal treatment that aims to reduce the proliferation of endometrial cells is promising, but there is a paucity of well-designed studies to guide treatment. There is a strong need to develop pharmacological agents that provide an efficient outcome (Farquhar et al, 2006). ABOUBAKR ELNASHAR
  25. 25. GnRHa: in adenomyosis (Wood et al, 2001). Constant hypoestrogenic state Amenorrhoea Control of pain Uterine shrinkage. But, pure antiestrogen may offer some advantage in the treatment of adenomyosis& trials are required to assess its usefulness. ABOUBAKR ELNASHAR
  26. 26. AI: in Leiomyoma (Parsanezhad et al,2010). Reduction of leiomyoma& uterine volumes GnRHa &AI concomitantly: in adenomyiosis (Kimura et al, 2007). Assuming aromatase production activity in the adenomyosis lesion This stimulated us to undergo this study GnRHa monthly for 12 w. ABOUBAKR ELNASHAR
  27. 27. 6. GnRHa administration before & during combination chemotherapy for breast cancer could preserve post-treatment ovarian function in women below 40 years GnRHa: 2 w before the initiation of chemotherapy Goserelin, 3.6 mg SC (Zoladex @, Zeneka Pharma International, UK) ABOUBAKR ELNASHAR
  28. 28.  GnRHa before & during combination chemotherapy for breast cancer: is feasible, well tolerated may preserve post-treatment ovarian function in women below 40 years. . ABOUBAKR ELNASHAR
  29. 29. ABOUBAKR ELNASHAR

×