Prevention of gonadal toxicity and preservation of gonadal function and fertility in young women with systemic lupus erythematosus treated by cyclophosphamide: the PREGO-Study.
BACKGROUND
With dramatically improved survival rates of SLE patients, comorbidity and long-term damage such as premature ovarian failure (POF) gain increasing importance. In the Erlangen cohort, 14% of cyclophosphamide treated patients younger than 41 years have POF, which is a common consequence of cyclophosphamide treatment.


METHODS
We tested the concentrations of FSH and LH, before, during and after cyclophosphamide treatment in 63 premenopausal women with SLE without ovarian protection and initiated the PREGO-Study (Prospective randomized study on protection against gonadal toxicity) in patients with SLE.


RESULTS
In lupus patients treated with cyclophosphamide, 60% suffered from POF and hypergonadotropic amenorrhea. Whereas the POF rate was <50% in women below 30 years, it was 60% between 30 and 40 years. The cumulative dosage of cyclophosphamide also strongly influenced POF rate.


CONCLUSIONS
Our present results, with a high POF rate in Cyclophosphamide treated SLE patients demonstrate the urgent need for ovarian protection in this patient group. Besides POF these women are at high risk for premature atherosclerosis which is the major cause of death in lupus. Following preliminary encouraging experience in women with lymphoma, in whom the temporary induction of a prepubertal hormonal milieu during chemotherapy, has significantly decreased the risk of POF, we have initiated the PREGO-Study, comparing randomised monthly injection versus no injection of gonadotropin-releasing hormone analogue (GnRH-a) to young SLE patients during cyclophosphamide therapy.
Manger
Karin
K
Department of Internal Medicine III and Institute for Clinical Rheumatology and Immunology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
Wildt
Ludwig
L
Kalden
Joachim R
JR
Manger
Bernhard
B
D000328:Adult; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy*; D007986:Luteinizing Hormone / Q000097:blood; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control*; D011446:Prospective Studies
D005300:Fertility Agents, Female; D007166:Immunosuppressive Agents; D007987:Gonadotropin-Releasing Hormone; D003520:Cyclophosphamide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone