What is the relationship between menstruation and proteinuria?

Menstruation Can Cause Transient Proteinuria Through Physiological Mechanisms

Menstruation can cause transient proteinuria due to hormonal fluctuations and physiological changes that occur during the menstrual cycle, but this is typically not clinically significant and should be considered when evaluating proteinuria in women of reproductive age. 1

Relationship Between Menstruation and Proteinuria

Physiological Mechanisms

• Hormonal influence: Estrogen and progesterone fluctuations during the menstrual cycle affect the renin-angiotensin-aldosterone system, which can temporarily alter glomerular filtration and protein excretion 1, 2
• Protein catabolism changes: Research has shown increased protein catabolism during the mid-luteal phase when estradiol and progesterone are high, leading to greater urinary urea nitrogen excretion compared to menses 3
• Posture-related effects: Proteinuria is sensitive to different postures (upright vs. recumbent), which may interact with menstrual cycle-related fluid shifts 4

Clinical Significance

• Menstruation is considered a benign cause of proteinuria that should be excluded when evaluating newly diagnosed asymptomatic microscopic hematuria 5
• Guidelines recognize menstruation as a potential confounding factor when assessing proteinuria, particularly in the context of pregnancy evaluation 1

Evaluation of Proteinuria in Women of Reproductive Age

Initial Assessment

• When proteinuria is detected in a woman of reproductive age, determine if testing coincided with menstruation
• If proteinuria is detected during menstruation, consider repeating the test after menstruation has ended 5
• For accurate assessment, use the protein-to-creatinine ratio in an untimed urine sample rather than 24-hour collections 5

Distinguishing Physiological from Pathological Proteinuria

• Physiological (menstruation-related):

  • Typically mild (<500 mg/24h)
  • Transient (resolves after menstruation)
  • Not associated with other signs of renal disease

• Pathological (requiring further evaluation):

  • Persistent proteinuria (present on multiple tests over time)
  • Significant proteinuria (>1000 mg/24h or >500 mg/24h if persistent)
  • Associated with hematuria, red cell casts, or renal insufficiency 5

Clinical Approach to Proteinuria in Menstruating Women

1. Initial detection of proteinuria:

   • Document menstrual status at time of collection
   • Use protein-to-creatinine ratio for quantification 5

2. If proteinuria detected during menstruation:

   • Repeat testing after menstruation has ended
   • If proteinuria resolves, it was likely menstruation-related

3. If proteinuria persists after menstruation:

   • Evaluate for other causes of proteinuria
   • Consider nephrology referral if:
     • Protein excretion >1000 mg/24h
     • Protein excretion >500 mg/24h if persistent or increasing
     • Presence of hematuria, red cell casts, or elevated creatinine 5

Special Considerations in Pregnancy

• In pregnant women, menstruation is absent but hormonal changes still affect protein excretion
• Gestational proteinuria (without hypertension) may be an early sign of preeclampsia 5, 1
• Protein-to-creatinine ratio ≥30 mg/mmol (0.3 mg/mg) is considered abnormal in pregnancy 1
• Women with gestational proteinuria should be monitored for development of preeclampsia 5, 1

Practical Recommendations

• When evaluating proteinuria in women of reproductive age, always document menstrual status
• Consider menstruation as a potential cause of transient, mild proteinuria
• If clinical decisions depend on accurate protein quantification, repeat testing after menstruation
• For research purposes, standardize collection times relative to menstrual cycle phases to minimize variability 2