Subclinical impairment of ovarian reserve in juvenile systemic lupus erythematosus after cyclophosphamide therapy

Clin Exp Rheumatol. May-Jun 2012;30(3):445-9. Epub 2012 Jun 26.


Objectives: To perform systematic assessment of ovarian reserve markers using a combination of tests in juvenile systemic lupus erythematosus (JSLE) patients without amenorrhoea.

Methods: Twenty-seven consecutive JSLE female patients and 13 healthy controls without amenorrhoea were evaluated for 6 months. Ovarian reserve was assessed during early follicular phase by serum levels of follicle stimulating hormone (FSH), luteinising hormone (LH), estradiol, inhibin A, inhibin B and anti-Mullerian hormone (AMH). Ovarian size was measured by abdominal ultrasonography. Demographic data, disease activity, damage and treatment were also analysed.

Results: The median of current age was similar in JSLE patients and controls (16.5 vs. 15years, p=0.31) with a significantly higher age at menarche (13 vs. 12years, p=0.03). A trend of lower median total antral follicle count was observed in JSLE compared to controls (9 vs. 14.5, p=0.062) with similar median of other ovarian reserve parameters (p>0.05). Further evaluation of patients treated with cyclophosphamide and those without this treatment revealed a higher median FSH levels (6.4 vs. 4.6 IU/L, p=0.023). Inhibin B, AMH levels and ovarian volume were also lower but did not reach statistical significance (10.8 vs. 27.6 pg/mL, p=0.175; 0.6 vs. 1.5 ng/mL, p=0.276; 3.4 vs. 5 cm3, p=0.133; respectively). LH (2.7 vs. 2.9 IU/L, p=0.43), estradiol (50 vs. 38 pg/mL, p=0.337) and inhibin A (1.1 vs. 0 pg/mL, p=0.489) levels were comparable in both groups.

Conclusions: Our study suggests that ovarian reserve after cyclophosphamide treatment may be hampered in spite of the presence of menstrual cycles emphasising the relevance of gonadal protection during the use of this alkylating agent.

MeSH terms

  • Adolescent
  • Anti-Mullerian Hormone / blood
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects
  • Child
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Estradiol / blood
  • Female
  • Follicle Stimulating Hormone / blood
  • Humans
  • Inhibins / blood
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / physiopathology
  • Luteinizing Hormone / blood
  • Menarche / drug effects
  • Menarche / physiology
  • Ovarian Diseases / blood
  • Ovarian Diseases / chemically induced*
  • Ovarian Diseases / physiopathology
  • Ovary / drug effects*
  • Ovary / physiology*
  • Young Adult


  • Antirheumatic Agents
  • inhibin A
  • inhibin B
  • Estradiol
  • Inhibins
  • Anti-Mullerian Hormone
  • Cyclophosphamide
  • Luteinizing Hormone
  • Follicle Stimulating Hormone