Pituitary-gonadal function in women following cyclophosphamide treatment for childhood nephrotic syndrome: long-term follow-up study

Abstract

Ovarian and pituitary-gonadal function was evaluated in 12 women who were treated with cyclophosphamide for nephrotic syndrome before or during puberty. The mean age at the start of treatment was 8.7 years; the mean total dose of cyclophosphamide was 439 mg/kg body weight; and the mean follow-up time was 12.3 years. The investigations included detailed developmental, menstrual and fertility histories; general and gynaecological examinations; basal levels and follicle-stimulating hormone and luteinizing hormone responses to gonadotropin-releasing hormone, and plasma oestradiol determinations. All patients had normal pubertal development and regular menstrual patterns. Two had borne healthy children. Although hormonal studies did not show obvious ovarian or pituitary-gonadal dysfunction, further follow-up is required to ascertain whether the patients with the most prolonged treatment undergo a premature menopause.

Children with Steroid-sensitive Nephrotic Syndrome Come of Age: Long-term Outcome

“…35,36 Female fertility seemed to be less affected by cytotoxic therapy in SSNS. 37,38 A recent meta-analysis recommended a supposedly safe cumulative dosage threshold below 300 mg/kg for a single course of CPO in males. 11 Some methodological problems remain unsolved: There is no definitive sperm count discerning fertile from nonfertile (healthy) men.…”

Alternative treatment to corticosteroids in steroid sensitive idiopathic nephrotic syndrome.

“…Second, the long term side effects of repeated courses of cytotoxic drugs are uncertain. In long term follow up, cyclophosphamide appears to be safe in terms of gonadal function in males and females in a cumulative dose of up to 500 mg/kg.22 23 For chlorambucil, a dose of less than 10 mg/kg seems to be safe whereas a dose of more than 18 mg/kg caused azoospermia in all boys. 24 The effects of sequential treatment with cyclophosphamide and chlorambucil are not known.…”

Pulse cyclophosphamide for steroid-resistant focal segmental glomerulosclerosis

“…The results for children with steroid-resistant nephrotic syndrome are not as promising [22,24]. Leukopenia, chemical cystitis, alopecia, and sterility pose considerable problems in patients exposed to prolonged courses of OCP [9,17,25,26]. A combination of pulse methylprednisolone and OCP has been advocated, but prolonged patient hospitalization and steroid side effects such as hypertension, cataracts, and growth retardation are problematic [9][10][11].…”

“…Future studies will have to examine possible impairment of fertility in our patients as a consequence of IVCP treatment. However, the cumulative doses given were far below those considered toxic [25,26]. Table 2 Comparison of responders and non-responders to IVCP therapy& / t b l .…”