Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy.
OBJECTIVE
To determine the risk for secondary amenorrhea after pulse cyclophosphamide therapy in premenopausal women with systemic lupus erythematosus.


METHODS
Controlled, retrospective clinical study.


METHODS
Government referral-based research hospital.


METHODS
Thirty-nine women younger than 40 years treated with pulse cyclophosphamide therapy for active lupus nephritis or neuropsychiatric lupus. Sixteen women who received pulses of intravenous methylprednisolone were controls.


METHODS
Sixteen patients received pulse cyclophosphamide (0.5 to 1.0 g/m2 body surface area) monthly for a total of 7 doses (short-CY), and 23 patients received 15 or more doses (long-CY). Control patients were treated with monthly pulses of methylprednisolone (1.0 g/m2) for a total of nine doses.


METHODS
Rates of amenorrhea were evaluated according to duration of treatment (number of doses) and age at the initiation of pulse therapy.


RESULTS
Two of 16 patients (12%) in the Short-CY group and 9 of 23 (39%) in the long-CY group developed sustained amenorrhea (P = 0.07). Rates of sustained amenorrhea (short- and long-CY) according to age at the start of pulse therapy were: < or = 25 years, 2/16 (12%); 26 to 30 years, 4/15 (27%); > or = 31 years, 5/8 (62%) (P = 0.04). The increased risk for sustained amenorrhea in patients treated with long-CY was most evident in patients older than 25 years (short-CY [2/12] compared with long-CY [7/11]; P = 0.03). Three other patients with short-CY had reversal of amenorrhea fewer than 12 months after cessation of therapy. Amenorrhea was not observed in any of the 16 control patients.


CONCLUSIONS
Intermittent pulse cyclophosphamide therapy in patients with systemic lupus erythematosus is associated with sustained amenorrhea, which is related to both age and number of doses of cyclophosphamide.
Boumpas
D T
DT
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
Austin
H A
HA
Vaughan
E M
EM
Yarboro
C H
CH
Klippel
J H
JH
Balow
J E
JE
D000328:Adult; D000367:Age Factors; D000568:Amenorrhea / Q000139:chemically induced*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D005298:Fertility / Q000187:drug effects; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008181:Lupus Nephritis / Q000188:drug therapy; D010053:Ovary / Q000187:drug effects; D012189:Retrospective Studies; D012307:Risk Factors
D003520:Cyclophosphamide