2L’ormone che induce il rilascio delle gonadotropine (GnRH) è il principale regolatore della cascata ormonale coivolta nella riproduzione ed è stato isolato dall’area preottica dell’ ipotalamo di mammiferi. E’ un decapeptide ed è rilasciato nel circolo sanguigno a livello della eminenza mediana in modo pulsatile di quantità precise dagli assoni di neuroni i cui terminali sono localizzati nell’ipofisi anteriore. Il rilascio di questo ormone avviene ogni minuti il quale regola la biosintesi e la liberazione di LH e FSH dall’ipofisi anteriore. La frequenza di rilascio del GnRH è massima durante l’ovulazione mentre è ridotta al minimo durante la fase luteale. La secrezione di GnRH e’ controllata negativamente da steroidi gonadici mentre neurotrasmettitori ad azione inibitoria quali il GABA, aminoacidi eccitatori (acido glutammico), peptidi oppioidi endogeni, monoamine del sistema noradrenergico, dopaminergico e serotoninergico, acetilcolina, melatonina, ossitocina modulano il rilascio di GnRH.
9Background Systematic reviews have found that luteinizing hormone – releasing hormone (LHRH) agonists are effectivein treating premenopausal women with early breast cancer.Methods We conducted long-term follow-up (median 12 years) of 2706 women in the Zoladex In premenopausal Patients (ZIPP), which evaluated the LHRH agonist goserelin (3.6 mg injection every 4 weeks) and tamoxifen (20 or 40 mg daily), given for 2 years. Women were randomly assigned to receive each therapy alone,both, or neither, after primary therapy (surgery with or without radiotherapy/chemotherapy). Hazard ratiosand absolute risk differences were used to assess the effect of goserelin treatment on event-free survival(breast cancer recurrence, new tumor or death), overall survival, risk of recurrence of breast cancer, andrisk of dying from breast cancer, in the presence or absence of tamoxifen.Results Fifteen years after the initiation of treatment, for every 100 women not given tamoxifen, there were 13.9 (95% confidence interval [CI] = 17.5 to 19.4) fewer events among those who were treated with goserelincompared with those who were not treated with goserelin. However, among women who did take tamoxifen,there were 2.8 fewer events (95% CI = 7.7 fewer to 2.0 more) per 100 women treated with goserelincompared with those not treated with goserelin. The risk of dying from breast cancer was also reduced at15 years: For every 100 women given goserelin, the number of breast cancer deaths was lower by 2.6(95% CI = 6.6 fewer to 2.1 more) and 8.5 (95% CI = 2.2 to 13.7) in those who did and did not take tamoxifen,respectively, although in the former group the difference was not statistically significant.Conclusions Two years of goserelin treatment was as effective as 2 years of tamoxifen treatment 15 years after starting therapy. In women who did not take tamoxifen, there was a large benefit of goserelin treatment on survival and recurrence, and in women who did take tamoxifen, there was a marginal potential benefit onthese outcomes when goserelin was added.
10Background: The usefulness of long-term, low-dose gonadotropin-releasing hormone agonist (GnRHa; buserelin acetate) therapy, so-called draw-back therapy, for the treatment of adenomyosis was investigated .Material/Methods: A retrospective observational study was conducted covering the period between January 2003 and March The subjects consisted of 12 patients with adenomyosis who underwent draw-back therapy for 2 years and had previously received GnRHa. GnRHa was initiated at 900 μg/day (6 nasalsprays/day). When the CA-125 level normalized, the GnRHa dosage was adjusted to 150–750 μg/dayto achieve a plasma estradiol (E2) concentration of 20–50 pg/ml (i.e., the therapeutic window).Pain during withdrawal bleeding and chronic pelvic pain were assessed using a visual analoguescale. In addition, bone mineral density (BMD) of the lumbar vertebrae was measured using dualenergyX-ray absorptiometry.Results: The mean GnRHa dose during draw-back therapy was 435 μg/day (2.9 nasal sprays/day). The meanE2 level during draw-back therapy was 36.3±14.3 pg/ml. The intensity of chronic pelvic pain wassignifi cantly lower during draw-back therapy than before draw-back therapy, and was nearly eliminatedin many patients (4.8±1.2 vs. 0.6±0.7, respectively [p=0.000]). Compared to the severity ofvasomotor symptoms during previous regular GnRHa therapy, the severity of vasomotor symptomsduring draw-back therapy was signifi cantly lower (3.8±0.7 vs 1.1±0.7, respectively [p=0.000]). Thedecrease in BMD during a 6-month course of treatment was 0.96±0.9%.Conclusions: GnRHa draw-back therapy allowed maintenance of plasma E2 levels within the therapeutic window.GnRHa can thus be administered for long periods of time while maintaining therapeutic effectson adenomyosis and suppressing adverse events.
11In the long-acting GnRHa group (GroupL), patients received 3 In the long-acting GnRHa group (GroupL), patients received 3.6 mg of subcutaneous goserelin acetate (Zoladex depot, AstraZeneca Ltd., Kings Langley, U.K.).In the short-acting GnRHa group (Group S), patients weresubcutaneously administered 0.5 mg of buserelin acetate(Superfact, Hoechst AG, Frankfurt, Germany) or leuprolideacetate (Lucrin, Labratories Abbot France, St. RemySur Avre, France) daily at hospital before human chorionicgonadotrophin (hCG) administration.
12During ovarian stimulation gonadotrophin-releasing hormone (GnRH) analogues are co-administered in order to prevent premature luteinizinghormone (LH) surges. Premature LH surges are observedin about 20% of stimulated cycles without using GnRHanalogues [2,3]. Avoiding the adverse effects of elevatedLH-levels, first GnRH agonist analogues were used to supplementthe gonadotrophin stimulation. The continuousadministration of GnRH agonists causes gonadotrophinsuppression through down-regulation and desensitizationof the GnRH receptors in the pituitary gland after aninitial short period of gonadotrophin hypersecretion .
15In this study, we aim to evaluate the clinical outcome and patient’s convenience of single administration of long-acting GnRHa (goserelin depot) as comparedwith multiple daily administrations of short-acting GnRHa (buserelin or leuprorelin).