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Morphologic changes in urine particles during the menstrual cycle.

To the Editor:

Our previous study demonstrated that the numbers of epithelial cells and erythrocytes in midstream urine vary significantly during the menstrual cycle (1). We now report the influence of the menstrual cycle on the number and morphology of urine particles.

Specimens were obtained from 67 healthy female students (age range, 18-20 years) at the College of Medical Technology. All participants gave written, informed consent; were asymptomatic; and provided information about their menstrual cycles.

None had urologic conditions at the time of the study. Participants were instructed to collect midstream urine samples in sterile containers. Particles in midstream urine were analyzed by use of a fully automated urine cell analyzer, the OF-100 (Sysmex Corporation), within 2 h of collection.

Specimens were classified into 3 groups according to the number of days after menstruation: menstrual (1-7 days after menstruation; n = 15), proliferative (8-14 days after; n = 24), and secretory (15-34 days; n = 22) phase.


Erythrocytes detected in the urine were classified into 2 groups, isomorphic and dysmorphic, according to the forward scattered-light intensity and distribution width. The OF-100 measures leukocyte size and counts small round epithelial cells by the forward scattered-light intensity.

The morphologic information obtained for urine particles in each phase is shown in Fig. 1. The frequency of isomorphic erythrocytes was significantly higher in the menstrual phase than in the other 2 phases, and almost all dysmorphic erythrocytes were observed in the proliferative and secretory phases (Fig. 1A). Leukocyte size was significantly larger in the menstrual phase than in the other 2 phases (Fig. 1B). The number of small, round epithelial cells gradually increased after menstruation and was significantly higher in the secretory phase (Fig. 1C).

Dysmorphic erythrocytes (morphologically variable) have been reported to be a marker for glomerular bleeding and isomorphic erythrocytes (morphologically uniform) for nonglomerular bleeding (2). The present study revealed that most erythrocytes in the menstrual phase are isomorphic but that all erythrocytes detected in the other phases are dysmorphic, suggesting the existence of dysmorphic erythrocytes in urine from healthy women, especially in the proliferative and secretory phases of the menstrual cycle.

Little is known about the usual variation in urinary leukocytes among healthy women. In the present study, leukocytes displayed significant size changes and were largest in the menstrual phase, decreasing in size thereafter. Recently reported cyclic changes in granulocyte colony-stimulating factor expression in the human follicle during the normal menstrual cycle (3) may be associated with our results, but the underlying mechanisms remain to be elucidated.

During the menstrual cycle, estrogen influences the proliferation and maturation of the vaginal epithelial cell layers during the proliferative phase, whereas progesterone is associated with shedding of the superficial epithelial cell layers during the secretory phase (4, 5). The number of small epithelial cells increases after menstruation and peaks in the secretory phase. Physiologic changes in vaginal secretions during the menstrual cycle could explain this.

In conclusion, although the number of participants was limited and an investigation of the same individuals during the menstrual phases will provide more appropriate and valid information, our results suggest an important influence of menstrual cycle on the morphology of urine particles.


(1.) Morimoto M, Yanai H, Shukuya K, Chiba H, Kobayashi K, Matsuno K. Effects of midstream collection and the menstrual cycle on urine particles and dipstick urinalysis among healthy females. Clin Chem 2003;49:188-90.

(2.) Apeland T. Flow cytometry of urinary erythrocytes for evaluating the source of haematuria. Scand J Urol Nephrol 1995;29:33-7.

(3.) Yanagi K, Makinoda S, Fujii R, Miyazaki S, Fujita S, Tomizawa H, et al. Cyclic changes of granulocyte colony-stimulating factor (G-CSF) mRNA in the human follicle during the normal menstrual cycle and immunolocalization of G-CSF protein. Hum Reprod 2002;17:3046-52.

(4.) Sjoberg I, Cajander S, Rylander E. Morphometric characteristics of the vaginal epithelium during the menstrual cycle. Gynecol Obstet Invest 1988;26:136-44.

(5.) Mauck CK, Callahan MM, Baker J, Arbogast K, Veazey R, Stock R, et al. The effect of one injection of Depo-Provera on the human vaginal epithelium and cervical ectopy. Contraception 1999;60:15-24.

Mie Morimoto [1] *

Hidekatsu Yanai [2]

Kazuhiko Matsuno [1]

[1] Department of Medical Technology Hokkaido University School of Medicine Sapporo, Japan

[2] Department of Internal Medicine Jikei University School of Medicine Chiba, Japan

* Address correspondence to this author at: Department of Medical Technology, Hokkaido University, School of Medicine, North-12, West-5, Sapporo 060-0812, Japan. Fax 81-11-706-4916; email

DOI: 10.1373/clinchem.2005.050419
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Title Annotation:Letters
Author:Morimoto, Mie; Yanai, Hidekatsu; Matsuno, Kazuhiko
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:Jun 1, 2005
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