The impact of cyclophosphamide on menstruation and pregnancy in women with rheumatologic disease.

Background: While cyclophosphamide (CYC) can save the life of a young woman with severe rheumatologic disease, it may lead to the long-term side-effects of infertility and premature menopause. We compared the reproductive health histories of young women with rheumatologic disease with and without prior CYC exposure to identify the impact of this medication on this important component of health.
Methods: This research includes a case-series study of women diagnosed with SLE, vasculitis, and scleroderma prior to age 35. Each patient completed a questionnaire about desired childbearing, menstrual regularity, infertility, and pregnancy history. Women with prior CYC therapy were queried about the use of gonadotropin-releasing hormone agonists (GnRH-a) for fertility preservation. The responses to this questionnaire were compared for women with and without CYC exposure.
Results: Of the 43 participants, 23 had prior CYC exposure and 20 were CYC naïve. The current age of these groups was similar (average age 32), but women with prior CYC were four years younger at diagnosis than women without CYC. More women with prior CYC had cessation of menses in the year prior to the study (30.4% vs 0%, p < 0.05). Of the women with prior CYC exposure, those with loss of menses were older at study enrollment, older at CYC treatment, and had a higher cumulative CYC dose than those with preserved menstruation. While more women with GnRH-a co-therapy during CYC had maintained menses, this difference did not reach statistical significance. Women with prior CYC without GnRH-a co-therapy had a higher frequency of nulliparity and had greater trouble conceiving than women with GnRH-a co-therapy. Few pregnancies were conceived following CYC exposure and all resulted in elective termination, miscarriage, or preterm birth.
Conclusion: In this cohort of young women with rheumatologic disease, more women with prior CYC than without had amenorrhea, nulliparity, and infertility. GnRH-a co-therapy may prevent these adverse effects of CYC.