Method: Twenty-seven consecutive JSLE female patients and 13 healthy subjects without amenorrhea (cessation of menstruation for more than 4 months after menarche) were evaluated prospectively for at least 6 months. Ovarian reserve was concomitantly assessed by serum levels of the following hormones (third to fifth day of the menstrual cycle): follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol by fluoroimmunoassay, and inhibin A, inhibin-B and anti-mullerian hormone (AMH) by enzyme-linked immunosorbent assay in duplicated samples. Ovarian size was measured by abdominal ultrasonography. Demographic data, disease activity score (SLEDAI), disease cumulative damage (SLICC/ACR-DI) and treatment of JSLE patients were also analyzed.
Result: The median of current age and body mass index were similar in JSLE patients and controls (16.5 vs. 15years, p=0.31; 23 vs. 22.4kg/m2, p=0.48). The age at menarche was significantly higher in JSLE patients that presented their first menstruation after disease onset versus controls (12.9 vs. 12years, p=0.044), whereas the frequencies of Tanner pattern 4 or 5 was similar in JSLE and controls (63% vs. 92%, p=0.07). The median levels of serum FSH (5.1 vs. 5.6IU/L, p=0.57), LH (2.7 vs. 3IU/L, p=0.8), estradiol (44.5 vs. 34pg/mL, p=0.37), inhibin A (0.3 vs. 0.1pg/mL, p=0.94), inhibin B (23.5 vs. 29.3pg/mL, p=0.58) and AMH (1.4 vs. 1.4ng/mL, p=0.7) were comparable in patients and controls. The median of ovarian volumes was also similar in JSLE versus controls (4.5 vs. 4.7cm3, p=0.1416). Eleven patients were under IVCYC with median duration time between the last dose and study entry of 2.5 years (range 0-7.7). Further evaluation of ovarian reserve revealed that the median levels of serum FSH was significantly higher in JSLE patients under IVCYC (n=11) compared to those without this treatment (n=16) (6.4 vs. 4.6IU/L, p=0.023), however the lower inhibin B and AMH levels, and ovarian volume in the former group did not reach statistical significance (10.8 vs. 27.6pg/mL, p=0.17; 0.6 vs. 1.5ng/mL, p=0.28; 3.5 vs. 4.6cm3, p=0.231; respectively). LH (2.7 vs. 2.9IU/L, p=0.43), estradiol (50 vs. 38pg/mL, p=0.34) and inhibin A (1.1 vs. 0pg/mL, p=0.49) levels were comparable in both groups. No correlation was found between FSH levels and duration of IVCYC use, inhibin A, inhibin B, AMH, SLEDAI and SLICC/ACR-DI in JSLE patients (p>0.05).
Conclusion: Our study suggest that ovarian reserve after cyclophosphamide treatment may be hampered in spite of menstrual cycles reinforcing the importance of gonadal function protection during the use of this alkylating agent. Further studies are necessary to determine the relevance of this subclinical condition for lupus fertility.
Disclosure: N. E. Aikawa, None; A. M. Sallum, None; R. M. R. Pereira, None, 2 ; E. Bonfa, None, 2 ; L. Suzuki, None; V. S. T. Viana, None; C. A. Silva, None, 2 .