Hormonal strategies for fertility preservation in patients receiving cyclophosphamide to treat glomerulonephritis: a nonrandomized trial and review of the literature

Abstract

Background: Prepubertal patients receiving chemotherapy are relatively resistant to cyclophosphamide-induced germinal cell alterations. We studied the possible protective effect of testosterone and triptorelin to inhibit gonadal activity in men and women receiving cyclophosphamide, respectively.

Study design: Nonrandomized trial.

Setting & participants: 28 consecutive patients, 11 men and 17 women, from a university medical center with various forms of glomerulonephritis, treated with cyclophosphamide.

Intervention: Men received cyclophosphamide plus testosterone; women were divided into 2 groups: 13 patients (group A) received cyclophosphamide plus triptorelin; 4 (group B) received only cyclophosphamide.

Outcomes & measurements: Serum follicle-stimulating hormone (FSH) and serum luteinizing hormone levels and, in addition, sperm counts and testosterone levels in men and estradiol levels in women were measured before and after treatment with cyclophosphamide.

Results: All 10 men became azoospermic or severely oligospermic during treatment; after 12 months, all except 1 had a normal sperm count and FSH levels were normal. In women during cyclophosphamide therapy, amenorrhea occurred in all patients. After cessation of therapy, all women in group A started to menstruate regularly, and at the end of follow-up, ovulatory cycles were demonstrated in all women. Hormone levels showed no significant changes throughout the observation period. Six women conceived, and the pregnancies were brought to term successfully without complications. In group B, all 4 women developed sustained amenorrhea; serum FSH and luteinizing hormone levels at the end of therapy and follow-up were significantly higher with respect to baseline; estradiol levels at the end of follow-up were significantly lower compared with baseline and corresponding values in group A.

Limitations: The substudy in men is uncontrolled, the substudy in women is nonrandomized.

Conclusions: The study suggests a protective effect of testosterone and triptorelin against cyclophosphamide-induced gonadal damage in men and women with various forms of kidney disease, respectively.