INVESTIGATIVE UROLOGY

Urinary glycosaminoglycan excretion during the menstrual cycle in normal young women
Maroclo MV, Pereira SD, Sampaio FJ, Cardoso LE
Urogenital Research Unit, State University of Rio de Janeiro, Rio de Janeiro, Brazil
J Urol. 2005; 173: 1789-92

• Purpose: We investigated whether the menstrual cycle affects urinary glycosaminoglycan (GAG) excretion in normal young women.
• Materials and Methods: Urine samples from 10 healthy women 19 to 21 years old were collected daily during the whole menstrual cycle. Concentration of total urinary GAG was assessed as µg hexuronic acid per mg creatinine. Proportions of sulfated GAG species were determined by agarose gel electrophoresis.
• Results: Mean excretion values +/- SD for period days 4 to 13 and 15 to 28 of the cycle were significantly different (0.445 +/- 0.041 vs 0.356 +/- 0.035 microg/mg, p < 0.001). Correlation between values for the first and second halves of the cycle showed that this difference was consistent irrespective of individual variations in GAG excretion (r = 0.9757, p < 0.001). Proportions of urinary sulfated GAG did not change during the cycle.
• Conclusions: Excretion of total urinary GAG during the normal menstrual cycle of young women has a biphasic pattern with significantly higher values occurring in the first half of the cycle. This variation implies modulation by estrogens and consequently it should be considered when comparing the GAG concentration in urine samples from women of childbearing age.
  
  
• Editorial Comment
  In the current study urine samples were obtained on a daily basis from a highly homogeneous group of donors. The authors isolated total GAG from these samples, thereby, eliminating other metabolites. The results showed a significant increase in total urinary GAG excretion in the first half of the cycle, which paralleled the normal increase in serum estrogen levels that occurs at this phase. In general, estrogen inhibits the synthesis of extracellular matrix molecules by many mesenchymal cell types, such as vascular smooth muscle cells. Such inhibition would shift normal proteoglycan turnover toward degradation, which could explain the increase in GAG urinary excretion that was found in the first half of the cycle.
  It was not observed significant variation in the relative concentration of sulfated GAG during the different phases of the cycle. On the other hand, the results indicate that heparan sulfate was the prevailing urinary GAG during the whole cycle. Because heparan sulfate is the most abundant GAG in the glomerulus, the present findings support the hypothesis that renal structures are one of the main sources of urinary GAG.
  Worth of attention, is the fact that pathogenesis of interstitial cystitis is usually related to alterations in the GAG urothelial layer, which would allow the permeation of irritant urinary components into the vesical wall. Several reports have shown abnormal urinary GAG excretion in patients with interstitial cystitis, although the results are conflicting. Accordingly, urinary GAG levels in female patients may be decreased, unaltered or significantly increased. In these reports controls usually consisted of urine samples from healthy women of childbearing age. However, the dates of the menstrual cycle in which these control samples were collected were not provided. Since the results of the present work indicate that urinary GAG excretion during the normal menstrual cycle has a significant and consistent variation, studies evaluating GAG excretion in women could lead to misleading or erroneous results if comparisons were made among samples taken from different phases of the cycle. This may be indeed the reason underlying the inconsistent results in previously published reports.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil