Ovarian Function And Fertility Preserved In Women With Severe Systemic Lupus Erythematosus

SLE, a complex and unpredictable autoimmune disease, is characterised by chronic inflammation and damage of body tissues, including the heart, lungs, kidneys, joints, and/or nervous system. It is most common in women and, although long-term survival has dramatically improved over time with better diagnosis and treatment options, one of the challenges in managing the disease is to minimise the side-effects of treatments such as the disruption of ovarian function and risks to fertility. Pulsed intravenous CYC, a chemotherapeutic agent, is a standard therapy for SLE but may also be associated with ovarian failure in addition to other adverse effects.

Dr Katerina Laskari, the presenting author of the study, led by Professor Athanasios G Tzioufas in the Department of Pathophysiology of the National and Kapodistrian University of Athens, said: "Although the prognosis for people with SLE has considerably improved over the years, a patient's quality of life can all too often be seriously impaired by the toxicity of many commonly-used treatments. Preserving ovarian function is a very important consideration in treating women with SLE of child-bearing age, who are already burdened by the difficult nature and impact of the disease itself."

In this retrospective evaluation of 61 postmenopausal women with SLE treated for lupus nephritis (n=58), autoimmune hemolytic anemia (n=1) and central nervous system involvement (n=2), 39 patients received prolonged treatment with 1g/m² intravenous (IV) CYC pulses (group A) for a median time of 24 months and 22 patients received 5-7 monthly 1g/m2 IV CYC pulses, followed by 2g/day MMF for a median time of 32 months (group B).

Results showed that disease activity was equally controlled using either treatment regimen (p=0.76 and p=0.31 for disease remission and relapse respectively), although patients in group A had a 4-fold higher risk of developing amenorrhea (absence of menstruation) compared with those in group B (p=0.001). 56% (n=22) of women in group A and 14% (n=3) in group B developed amenorrhea, while sustained amenorrhea developed in 51% (n=20/39) of women in group A vs 4% (n=1) in group B. 14% (3/22) of women in group A and 67% (2/3) in group B resumed menstruation following cessation of therapy.

Age (p<0.001), cumulative CYC dose (p=0.001) and anti-Ro antibodies (p=0.002) were significant in terms of amenorrhea. Sustained amenorrhea was related to both the form of treatment (p=0.006) and the age of the patients (p=0.026). The median total CYC dose until amenorrhea was 11 gr (range 2-29.5) and 3.7 gr (range 2-6.75) in group A and B respectively (p=0.036).

The median age of women with amenorrhea was 36 years (range 19-46) in group A and 33 years (range 27-45) in group B (p=0.71). It is of note that all patients aged >31 years developed amenorrhea with the long course CYC treatment and 94% did not resume menses until the end of follow up, whereas only 1 patient aged 45 years developed permanent amenorrhea with the short course CYC treatment.

SLE disease duration and ECLAM (European Consensus Lupus Activity Measurement) score were not significantly different in terms of amenorrhea (pe0.05).