Estrone-3-Glucuronide (E1G) Rise in the Luteal Phase
Yes, E1G levels do rise again during the mid-luteal phase (approximately 7-10 days post-ovulation peak), reaching levels that are approximately 2-3 times higher than early follicular phase baseline values. 1
Biphasic Pattern of E1G During the Menstrual Cycle
E1G exhibits a characteristic biphasic pattern throughout the menstrual cycle that mirrors estrogen activity:
First Peak (Pre-Ovulatory)
- E1G rises sharply during the late follicular phase, reaching peak levels approximately 1 day after the plasma estradiol peak and typically 1 day before or coinciding with the LH surge 2, 3
- This pre-ovulatory E1G peak represents maximal follicular estrogen production and provides direct measurement of follicular growth 4
- Peak E1G concentrations during this phase average approximately 106 nmol/L (range 78-137 nmol/L) 3
Second Rise (Mid-Luteal Phase)
- During the luteal phase, estrogen levels rise again as the corpus luteum produces both progesterone and estrogen, resulting in a secondary elevation of E1G 1, 5
- This second rise occurs approximately 7-10 days after the initial E1G peak (corresponding to the mid-luteal phase) 1
- When estrogen levels recede at the end of the luteal phase, menstruation occurs 1
Magnitude of Luteal Phase E1G Elevation
The luteal phase E1G rise represents a 7-fold increase from early follicular phase baseline values to peak luteal phase levels 2:
- Early follicular phase baseline E1G levels are relatively low
- The luteal phase E1G elevation typically reaches approximately 2-3 times the early follicular baseline, though still lower than the pre-ovulatory peak 2
- This represents the corpus luteum's continued estrogen production alongside progesterone secretion
Clinical Significance
Physiological Effects
- The elevated estrogen during the luteal phase has important metabolic effects, including protein-sparing during exercise, improved glucose metabolism, and increased lipid oxidation 1, 5
- Estrogen during this phase improves muscle strength and bone mineral density 1
- The combination of elevated estrogen and progesterone leads to increased fluid retention 1, 5
Monitoring Ovarian Function
- Daily E1G monitoring provides real-time assessment of ovarian activity and can distinguish between anovulatory cycles, cycles with luteinized unruptured follicles, and normal ovulatory cycles 4
- The ratio of E1G to creatinine in morning urine provides the most reliable measurement, reducing day-to-day variation from approximately 40% to 25% 2
- The sustained rise in E1G (calculated using cumulative sum methods) is superior to other indices for determining the first significant rise in a cycle 2
Important Caveats
- Individual cycle length significantly affects the timing of both E1G peaks: women with 22-day cycles will have earlier peaks compared to those with 35-day cycles 1
- The luteal phase E1G rise is less pronounced than the pre-ovulatory peak but remains clinically significant for assessing corpus luteum function 2
- Measurement should ideally be corrected for urinary creatinine concentration to account for hydration status and improve reliability 2