Masala A, Faedda R, Alagna S, Satta S, Chiarelli G, et al
Use of testosterone to prevent cyclophosphamide-induced
Ann Int Med
(Feb) 126:292-295 1997
The alkylating agent cyclophosphamide (CPA) has been used successfully
in the treatment of a number of glomerular diseases. A major factor
limiting its use is the frequent development of gonadal toxicity. These
investigators designed a pilot study to test the hypothesis that
testosterone (TES) would lower activity of germinal cells in men aged
23-35 and thereby preserve sperm producing capacity. Study subjects,
all with glomerulonephritides, were divided into groups of 5 patients
each. Group A received 150 mg daily oral CPA for 6-8 months, group B
and C received 15 mg/kg intravenous boluses of CPA monthly for 6-8
months. In addition, the 5 patients in group C also received
testosterone 150 mg intramuscularly every 15 days, starting 30 days
before CPA therapy. Baseline characteristics were similar between
groups, but 6 months after treatment there was a marked reduction in
follicle-stimulating hormone levels in the TES treated group and sperm
counts were within normal limits (45.78 +/- 3.89 x 1000,000/mL). In
comparison, FSH levels were markedly elevated and only 1 of 10 patients
had a normal sperm count 6 months after treatment with CPA without TES.
Lutenizing hormone levels remained unchanged, and there were no side
effects related to TES use in this study. All patients had clinical
remission of their renal disease.
Comment: This pilot study is most encouraging for clinicians who
treat males with future reproductive potential with cyclophosphamide.
Coverage during cytotoxic treatment with testosterone may afford safe
and effective gonadal protection, thus allowing us to increase the use
of cyclophosphamide. Amazingly, all 15 patients with various forms of
GN in this study got better with cytotoxics. This and future similar
studies in males and females deserve our close attention.
(Sri Narsipur, MD, SUNY-HSC at Syracuse, NY)