Discussion
breast cancers, breast cancer, cancer, cognitive problems, prostate, uterine, and ovarian cancers, depression, vaginal dryness
PREMATURE PUBERTY, STILL, ABNORMAL UTERINE BLEEDING, BREAST CANCER, SIDE EFFECT, CANCER, DRUG SIDE EFFECTS, REGRESSION, DISEASES, COMPLICATIONS
Given the rising trend of breast cancer in the world and in Iran and the ensuing widespread use of GnRH agonists by these patients, physicians and patients must have access to products with the least side effects and the greatest effectiveness. This non-inferiority RCT aimed to compare the effectiveness of two injectable medications, i.e., one-month and three-month Microrelin (Homa Pharmed Company) and three-month Diphereline (IPSEN France), in terms of estrogen and FSH reduction as well as the occurrence of menopause complications and symptoms. Examining the changes in the variables over one year showed that the variations in estradiol and FSH levels as well as the drug side effects and symptoms of menopause did not differ significantly in Microrelin 3.75 and 11.25 mg groups compared to the Diphereline group and they can be considered in Iranian patients’ treatment.During the study period of one year, a decreasing trend was observed in serum FSH and estradiol levels in all three treatment arms. Bellet et al. examined 116 premenopausal patients with breast cancer. After the patients received triptorelin, the estradiol level decreased by more than 95% in months 3, 6, and 12 compared to the outset of the study [Some factors such as the type of chemotherapy regimen, estrogen agonist drugs, and the time of GnRH agonist administration (which can be simultaneously with or after the chemotherapy drug) may affect the performance of the drug and its effectiveness in reducing ovarian function. Still, despite the presence of other factors influencing the effectiveness of cancer treatment, the results of the present study confirmed the effect of all three drugs on FSH and estradiol reduction. Only the level of FSH in the 9th month was slightly lower in the Diphereline group than in the other two groups (P = 0.006), although this finding did not have a marked effect on the overall results of the study, i.e. the comparison of the efficacy and side effects of the three studied drugs over one year. Investigating potential influencing and confounding factors in the effectiveness of GnRH agonists certainly requires independent, extensive, and controlled studies. The effectiveness of the three drugs over time was compared using linear regression and by adjusting the effect of group and time. The results showed that the mean serum estradiol and FSH level reduced by 0.521 and 0.88 units more with Microrelin 3.75 mg injection over three months compared to Diphereline. The injection of Microrelin 11.25 mg also reduced FSH level by 1.25 units more than Diphereline, but it decreased the estradiol level less by 0.66 units. Since the mentioned variations were not significant at the 5% level and showed a very small difference in the one-year efficacy trend curve, the lack of superiority in the efficacy of Diphereline compared to the two Microrelin drugs manufactured in Iran can be confirmed.Therefore, to save foreign exchange costs, reduce the treatment costs of breast cancer, and due to the cost-effectiveness of the two similar drugs manufactured by Homa Pharmed Company, the use of the Iranian GnRH agonist is recommended. Note that GnRH agonists are also administered in the treatment of other diseases such as abnormal uterine bleeding, premature puberty, and prostate, uterine, and ovarian cancers; therefore, the approval of domestic drugs can save costs and develop domestic pharmaceutical industries.The drug efficacy diagram (Fig. The findings of this study showed that during the course of the study, the mean score of total menopausal symptoms increased significantly in all three groups, which demonstrates the effect of all three drugs on the induction of menopause and its symptoms. Still, in none of the three groups was there any specific side effect that led to drug discontinuation, hospitalization, or exclusion from the study –an observation that emphasizes the safety of the two domestically-manufactured drugs. Menopause involves physical symptoms such as hot flashes, psychological symptoms such as depression, cognitive problems, and urinary-reproductive symptoms such as vaginal dryness [This randomized clinical trial was achieved in a breast cancer center in Tehran which their patients were referred from different cities of Iran. It seems that hormonal effect of the studied three GnRH agonists drugs can be generalized to the breast cancers of other centers in this country. Studying the long-term effect of these drugs in future researches can provide valuable evidences for planning the breast cancer treatment protocol in premenopausal women.