Evidence suggests that it is possible to shield vulnerable organs such as the ovaries from the damaging effects of cancer treatments Viagra pharmacy in Canada. The ovaries can be surgically moved out of the direct path of radiation exposure. Ovarian transposition can be to an alternative location in the abdomen or to a heterotopic site such as the forearm. While this ovarian transposition has been used in adults with limited success, it is not a long-term solution for the preservation of fertility in younger patients.
An alternative protective approach, which is suitable for girls, is based on the idea that the pre-pubertal ovary is relatively quiescent and can be pharmacologically protected from the cytotoxic effects of medical therapies that destroy rapidly dividing cells. The drugs that can be used to limit the gonadal toxicity of otherwise successful treatments include gonadotrophin-releasing hormone (GnRH) agonists and antagonists. These synthetic hormones are based on the endogenous brain peptide GnRH and are routinely used in reproductive medicine to reversibly shut down ovarian function and induce a hypogonadotrophic2 state. In the context of shielding the ovary of a young patient, the GnRH analogue would be administered before the start of chemo- or radiotherapy to suppress the release of the follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the brain. FSH and LH normally drive cell division and pro-mote growth in ovarian follicles. If the cells in the follicle are actively dividing, they are more vulnerable to the cytotoxic damage by chemo- or radiotherapy treatments. Administration of drugs such as GnRH agonists during treatment would therefore be expected to protect the ovaries by inhibiting the later stages of follicle growth. In support of this idea, Ataya et al. demonstrated in primates that GnRH-agonist co-treatment protected the Rhesus monkey from cyclophosphamide (an alkylating agent) induced ovarian damage. These findings are supported by several clinical studies. For example, co-treatment with GnRH agonist during chemotherapy resulted in premature ovarian failure in only 2.3 per cent of patients compared with 58 per cent in the group treated with chemotherapy only. GnRH agonist administration to adolescents during chemotherapy has also been shown to confer some degree of protection on the ovary. While these studies are encouraging, conflicting evidence raises doubts as to the benefit of this approach and for the most part the data remain unconvincing.
Programmed cell death by apoptosis has been identified as the mechanism responsible for both the loss of oocytes that occurs during the normal process of oogenesis (the process by which mature ova are produced in the ovary) and for oocyte loss induced by anti-cancer therapies. Preliminary evidence has implicated sphingosine3-based lipid signalling molecules such as ceramide and sphingosine-1-phosphate (SIP) as key mediators of cellular growth, differentiation and apoptosis in postnatal ovaries. This observation has opened new avenues for protecting the ovaries of patients from possible side-effect damage. Treatment of mouse ovaries in vitro with SIP resisted the apoptosis induced by anticancer therapy, whereas in vivo injection of SIP into the ovarian bursa of mice completely prevented radiation-induced oocyte loss. Further research is required to explore the potential protective effect of small lipid molecule therapy on the ovaries of young patients.