Is the co-administration of a protective drug useful?
What is a protective drug?
It is known that the Chemotherapy leads to a risk of ovarian failure of about 40% in women of reproductive age, which can be as high as 100% when given in combination in preparation for a bone marrow transplant. A protective drug would be one that reduces the destruction of eggs during chemotherapy treatment, thus avoiding the risk of ovarian failure. Ovarian failure is clinically manifested by the definitive absence of menstruation, associated with hormonal markers in the blood that confirm the absence of ovarian function.
Co-administration of various drugs during chemotherapy has been tested. Among the most evaluated are the GnRH agonists, which, due to their effect of inhibiting ovulation by blocking the secretion of hormones in the brain, could make the ovary less vulnerable to the toxic effect of chemotherapy and especially of a subgroup that includes alkylating agents, including cyclophosphamide.
Scientific Evidence
A recent meta-analysis compiled studies published between 1966 and 2007 in women of reproductive age with cancer or autoimmune diseases who were given chemotherapy with or without GnRh analog (aGnRH) and evaluated their effect on ovarian preservation. Ovarian preservation was defined as the restart of menstrual cycles and hormonal normalization after chemotherapy; The presence of fertility was defined as the possibility of achieving a pregnancy after treatment.
Out of a total of 62 studies evaluated, 9 were included in the meta-analysis. 93% of the 178 women who received aGnRH during chemotherapy retained their ovarian function. Only 48% of the 188 women not treated with aGnRHa retained ovarian function. Additionally, 22% of women in the aGnRH group became pregnant compared to 14% in the control group, equivalent to a 65% increase in the probability of pregnancy.
The evidence suggests that premenopausal women undergoing chemotherapy should receive fertility preservation counseling, including the use of aGnRH
Dosage
The GnRH analogue should be started ten to fifteen days before the start of chemotherapy and should be continued for the duration of chemotherapy. The form of parenteral (intramuscular or subcutaneous) application as well as the frequency of application will be determined by the commercial presentation of aGnRH.
Mechanism of Action
A few years ago we conducted a study in rats to evaluate whether surgical removal of the pituitary gland had the same effect as aGnRH in preventing the destruction of eggs caused by chemotherapy.
To this end, it was submitted to He studied 40 Sprague-Dawley rats, half of which had their pituitary glands removed (hypox). In addition, half of the rats in each group were treated with aGnRH for fifteen days before a single dose of cyclophosphamide (CTX), which in turn was administered to half of the rats in each subgroup. Ten days later, the rats were euthanized in order to evaluate the effect of chemotherapy on the eight subgroups.
Cyclophosphamide was observed to significantly decrease the number of follicles or eggs in ovarian tissue. Both hypophysectomy and previous administration of aGnRH had an independent protective effect on the number of remaining follicles in the ovary, however, an additive protective effect was observed in the subgroup of hypophysectomized animals that additionally received aGnRH with respect to the group that only received aGnRH ((32.7 + 4 vs. 15.9 + 1.9 follicles per ovarian section, p<.001). It was concluded that the protective effect of aGnRH goes beyond severe pituitary suppression, and may be mediated by their effect elsewhere, perhaps directly in the ovary.
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GroupArticle for El Colombiano’s blog Let’s Talk About Fertility
