Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus.
OBJECTIVE
Cyclophosphamide (CYC) therapy for systemic lupus erythematosus (SLE), a disease predominantly affecting women of childbearing age, causes an unacceptably high incidence of irreversible premature ovarian failure (POF). This study was performed to evaluate the effectiveness of depot leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a), for protection against POF during CYC therapy.


METHODS
Young women with severe SLE treated in a standardized protocol of monthly intravenous bolus CYC were offered treatment with GnRH-a (depot leuprolide acetate; a 3.75-mg monthly injection during the standard CYC regimen). Patients treated with GnRH-a were compared with controls individually matched by age (+/-5 years) and by cumulative CYC dose (+/-5 gm). Reproductive status was determined after a minimum followup of 3 years after CYC therapy. The primary outcome was time to POF. Paired summary statistical analyses, Kaplan-Meier survival estimates, and Cox regression analyses were performed to assess differences in outcome between groups.


RESULTS
POF developed in 1 of 20 women treated with GnRH-a (5%) compared with 6 of 20 controls (30%) matched by age and cumulative CYC dose (matched odds ratio 0.09, P < 0.05). Kaplan-Meier estimates demonstrated improved cumulative ovarian protection over time in the GnRH-a-treated group (P = 0.04).


CONCLUSIONS
Treatment with GnRH-a during CYC therapy was associated with a significant reduction of POF in young women with severe SLE.
Somers
Emily C
EC
University of Michigan Health System, Ann Arbor, USA.
Marder
Wendy
W
Christman
Gregory M
GM
Ognenovski
Vladimir
V
McCune
W Joseph
WJ
D000328:Adult; D003520:Cyclophosphamide / Q000009:adverse effects*; D003627:Data Interpretation, Statistical; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016729:Leuprolide / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D010053:Ovary / Q000187:drug effects / Q000503:physiopathology; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D016019:Survival Analysis; D016896:Treatment Outcome
D005300:Fertility Agents, Female; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D005640:Follicle Stimulating Hormone; D016729:Leuprolide