Protection from Cyclophosphamide-induced Testicular Damage with an Analogue of Gonadotropin-releasing Hormone

How to Preserve Fertility in Young Women Exposed to Chemotherapy? The Role of GnRH Agonist Cotreatment in Addition to Cryopreservation of Embrya, Oocytes, or Ovaries

“…The possibility of administering an adjuvant treatment that may minimize the gonadal damage caused by an otherwise successful treatment program is obviously very attractive [1][2][3][4][5][6][7]. Glode et al [8] tested this hypothesis using a murine model and concluded that an agonistic analogue of GnRH appeared to protect male mice from the gonadal damage normally produced by cyclophosphamide [1]. Although previous suggestions have been made [1,9] claiming that primordial germ cells fare better than germ cells that are part of an active cell cycle, this hypothesis has not been seriously tested clinically, until recently [1, 4, 7, 10 -12].…”

“…Although previous suggestions have been made [1,9] claiming that primordial germ cells fare better than germ cells that are part of an active cell cycle, this hypothesis has not been seriously tested clinically, until recently [1, 4, 7, 10 -12]. Whereas several investigators have demonstrated that GnRH agonists inhibit chemotherapyinduced ovarian follicular depletion in the rat [8], uncertainty remains regarding human application [1,4,[5][6][7][8][9][10][11][12]. The human ovary has lower concentrations of ovarian GnRH receptors and may not necessarily exhibit the same response as the rat ovary [1,4,[5][6][7][8][9][10][11][12].…”

Protection of rat spermatogenic epithelium from damage induced by procarbazine chemotherapy

“…In rats, recovery from nitrofuran toxicity is hastened by pretreatment with testosterone or oestradiol (Nelson et al, 1954). In preliminary experiments, we demonstrated partial testicular protection in mice from very toxic (>LD50) doses of cyclophosphamide, but we and others were unable to produce permanent infertility or demonstrate consistent protection with this model (Glode et al, 1981(Glode et al, , 1982da Cunha et al, 1987).…”

Hypogonadotrophism fails to prevent severe testicular damage induced by total body irradiation in a patient with beta-thalassaemia major and acute lymphoblastic leukaemia

“…However, these data cannot be extrapolated to adult thalassaemics with HH. Pre-pubertal and peri-pubertal children have immature hypothalamic-pituitary-gonadal axes and suffer less gonadal damage than the adults, as evident from the original work of Glode et al 2 Additionally, the conditioning regimens used in these studies included chemotherapeutic agents and not TBI.…”

“…1 The concept of protection of spermatogenic function from cytotoxic damage stems from the original study of Glode et al, 2 who showed gonadal protection in a prepubertal mouse model by administering gonadotrophin-releasing hormone (GnRH)-agonist during and after cyclophosphamide treatment which is presumed to result in a resting testicular state, thereby rendering spermatogonia quiescent and resistant to chemotherapy. There is no human study to determine the effect of GnRHagonist towards preventing gonadal damage following radiotherapy, and only conflicting results 3,4 are available from animal studies.…”