GnRH agonist In Gynaecology (GnRHa)

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

Physiology &Action
Native form: synthesized in hypothalamus acts on pituitary, results in LH FSH GnRH Agonist: initial stimulation effect. 1. Sustained exposure Leads to down regulation of Pituitary target cells (ca++ receptors) FSH&LH. Results in Gonadal steroidogenesis. 2. Longer life, and bioviability. 150-300 active than native form. Differ with the preparation.

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

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

Contra-indications
Pregnancy Breast feeding Undiagnosed vaginal bleeding

Clinical Application(1)
1. 2. 3. 4. 5. 6. 7. General Gynaecology: Endometriosis Uterine fibroids DUB Central precocious puberty Premenstrual syndrome Hyperandrogenism (PCOS,Hirsutism) Chronic Pelvic pain

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 <10% size reduction)

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 >12 weeks growth to previous size. Subserosal ? Necrosis & acute presentation.

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

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

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)

Chronic Pelvic Pain

Common Gynaecological problem
Residual ovary syndrome Pelvic congestion syndrome

GnRHa:*reduces vascularity&inflammation *Suppress ovulation, prevents capsular expansion & reduces ovulation pain HRT add back

PMS
Aetiology?? Cyclical symptoms: psychological, behavioural, and somatic Conventional treatment:???. Ovariectomy

GnRHa: medical ovariectomy

Diagnostic. Not with affective disorder Duration:3-6/month,add back HRT May precipitate depression (original symptom!)

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 : > 12 months

Hyprandrogenism
GnHRa :reduces serum testosterone & androsteroidione 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.

Clinical Application (2)

1. 2. 3. Infertility : Ovulation induction Stimulation for IVF cycles Trigger of ovulation( to prevent OHSS)

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

Infertility (cont)
Trigger of ovulation: instead of HCG.single or double doses.usually intranasal
Longer 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

Clinical Application (3)

Oncology:
1. Breast malignancy 2. Ovarian malignancy 3. Endometrial malignancy

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

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.