GnRH agonist In Gynaecology (GnRHa)

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GnRH agonist In Gynaecology(GnRHa)

• Dr. Salah Baloul MRCOG
• Consultant Obstetrician Gynaecologist
• Taif Maternity Hospt ,K.S.A

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Physiology Action

• Native form synthesized in hypothalamus acts on
  pituitary, results in LH FSH
• GnRH Agonist initial stimulation effect.
• Sustained exposure Leads to down regulation of
  Pituitary target cells (ca receptors)
  FSHLH. Results in Gonadal steroidogenesis.
• Longer ½ life, and bioviability. 150-300 active
  than native form. Differ with the preparation.

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Preparations

• Different preparations.Nona and Deca peptides
• Different doses depends on preparation, route
  of administration(Sub/c injection or implants,
  I.M and intranasal .. commonest) e.g Nafarelin,
  Buserlin, Goserelin, Leuprorelin)
• New preparations works for up to 90 days

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Side Effects

• Breakthrough bleeding (initially)
• Hypoesterogenic Status Hot flushes,
  palpitations, increased sweating, vaginal
  dryness, change of libido, headache or migraine.
• Osteoporosis Duration dependant, 6 possible
  loss, reversible

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Contra-indications

• Pregnancy
• Breast feeding
• Undiagnosed vaginal bleeding

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Clinical Application(1)

• General Gynaecology
• Endometriosis
• Uterine fibroids
• DUB
• Central precocious puberty
• Premenstrual syndrome
• Hyperandrogenism (PCOS,Hirsutism)
• Chronic Pelvic pain

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Uterine fibroids

• Before hysterectomy reduces size by 50.
  Correction of anaemia (6.4 to 13.2 gm/dl).vaginal
  feasibility up to 18l52 size.
• Before hysteroscopic surgery 38 size reduction,
  reduces fluid load risk,HB correction. Possible
  stromal tumour detection(no or lt10 size
  reduction)

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Uterine fibroids cont

• Before myomectomy reduces tumour size, intra
  operative bleeding, and p.operative morbidity.
• No effect on dissection or enucleation.
• Duration 8-12 weeks maximum benefit.delay of
  surgery for gt12 weeks growth to previous
  size.
• Subserosal ? Necrosis acute presentation.

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Endometriosis

• Growth associated with oesrogen cyclical
  ovarian steroids .
• Presentation
• Symptoatic usually pain. Depends on site of
  implants. Dysmenorrhea. Post coital, pelvic,etc
• Ovarian cyst
• Infertility

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Endometriosis 2

• GnRHa
• superior to other medications in symptomatic
  patients clinically objectively and in number
  of patients withdrawal.
• In ovarian cyst and implants reduces vasculation
  , pelvic inflammation and size
• Infertility the contribution of the disease
  itself in infertility depends on its extent.
• Add back

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Dysfunctional uterine bleeding

• Indications for GnHRa
• Failure of conventional treatment
• Pre operative hysterectomy
  Endometrial ablation or TCRE ( Render endometrium
  atrophic and reduces operative time fluid load
  risk)

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Chronic Pelvic Pain

• Common Gynaecological problem
• Residual ovary syndrome
• Pelvic congestion syndrome
• GnRHareduces vascularityinflammation
• Suppress ovulation, prevents capsular
  expansion reduces ovulation pain
• HRT add back

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PMS

• Aetiology??
• Cyclical symptoms psychological, behavioural,
  and somatic
• Conventional treatment???. Ovariectomy
• GnRHa medical ovariectomy
• Diagnostic. Not with affective disorder
• Duration3-6/month,add back HRT
• May precipitate depression (original symptom!)

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Central precocious puberty

• Idiopathic CPP( GnRH dependant)
• Peripheral PP ( GnRH independent)
• Problems Sexual maturation,
  Rapid bone growth
• GnRHa Slows sexual development without
  compromise of sexual potential .
  Arrest and normalization of bone growth
  Safe , effective and reversible
• Duration gt 12 months

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Hyprandrogenism

• GnHRa reduces serum testosterone andr-
  osteroidione 50. No effect on DHES
  (adrenal).Ovaries has minimal contribution.
• Has a place in Idiopathic Hirsutism and PCOS (
  Not entirely ovarian). Other drugs are more
  acceptable.

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Clinical Application (2)

• Infertility
• Ovulation induction
• Stimulation for IVF cycles
• Trigger of ovulation( to prevent OHSS)

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infertility

• In ovulation induction IVF cycles
• just prior to HCG use
• requires luteal phase support
• Advantage
• Avoidance of premature LH surge
• synchronization of follicular growth. Hence
  improves quality of ovum collection
• Organization of cycles and less cancellation

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Infertility (cont)

• Trigger of ovulation instead of HCG.single or
  double doses.usually intranasal
• Longer ½ life results in less luteotrophic
  effect development of multiple corpora lutea
• May reduce the risk of OHSS.
• Prerequisite No prior use of GnRHa in the
  cycle.infertility not related to GnRHa deficiency
• Pulsatile GnRHa in cycle stimulation

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Clinical Application (3)

• Oncology
• Breast malignancy
• Ovarian malignancy
• Endometrial malignancy

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• BREAST as adjuvant therapy with wide local
  incision in premenoupasl. Palliative in advance
  cases( pre postmenopasusal pts)
• OVARIANEpithelial tumours ,advance cases or
  refractory after chemotherapy.
• ENDOMETRIAL metastaic advance cases.
  (progesterone oestrogen receptors ve)

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Conclusion

• Different preparation with different bioviability
  and half life.
• Requires sustained release to result in down
  regulation effect,and medical ovariectomy.
• Duration is limited by side effects.
• Add back therapy may be required.
• GnRH antagonists may take over its action.