Normal Hormone Levels and Ratios Throughout the Female Menstrual Cycle
The optimal levels of estradiol, progesterone, and testosterone vary significantly throughout the menstrual cycle, with estradiol peaking at midcycle (275-2864 pmol/L), progesterone reaching maximum levels during the mid-luteal phase, and testosterone showing modest fluctuations with a slight midcycle elevation. 1, 2
Estradiol Levels Throughout the Menstrual Cycle
Estradiol levels fluctuate significantly during the menstrual cycle, with reference ranges established using highly accurate LC-MS/MS methods:
- Early Follicular Phase (days -15 to -6): 31-771 pmol/L (8-210 pg/mL)
- Late Follicular Phase (days -5 to -1): 104-1742 pmol/L (28-474 pg/mL)
- LH Peak/Ovulation (day 0): 275-2864 pmol/L (75-780 pg/mL)
- Early Luteal Phase (days +1 to +4): 95-1188 pmol/L (26-324 pg/mL)
- Mid Luteal Phase (days +5 to +9): 151-1941 pmol/L (41-529 pg/mL)
- Late Luteal Phase (days +10 to +14): 39-1769 pmol/L (11-482 pg/mL) 1
Progesterone Levels Throughout the Menstrual Cycle
Progesterone levels remain relatively low during the follicular phase but increase dramatically after ovulation:
- Follicular Phase: <3 ng/mL (typically 0.1-1.5 ng/mL)
- Ovulation: Begins to rise
- Mid-Luteal Phase: 7-20 ng/mL (peak levels)
- Late Luteal Phase: Begins to decline if no pregnancy occurs 3
Testosterone Levels Throughout the Menstrual Cycle
Testosterone shows less dramatic fluctuations compared to estradiol and progesterone:
- Reference Range (overall): 15-46 ng/dL (520-1595 pmol/L)
- Free Testosterone: 1.2-6.4 pg/mL (4.16-22.2 pmol/L)
- Bioavailable Testosterone: 1.12-7.62 ng/dL (38.8-264.21 pmol/L) 4
Testosterone levels show a modest increase at midcycle but this increase is relatively small compared to the overall variability 4, 2. Free testosterone levels tend to increase from the follicular to luteal phase as the percentage of free testosterone increases, despite total testosterone showing a progressive decline through the cycle 5.
Hormone Ratios Throughout the Menstrual Cycle
The ratios between these hormones shift dramatically throughout the cycle:
Follicular Phase
- Estradiol:Progesterone ratio: High (estradiol dominant)
- Estradiol:Testosterone ratio: Moderate
- Characterized by rising estradiol and low progesterone
Ovulatory Phase
- Estradiol:Progesterone ratio: Highest (peak estradiol)
- Estradiol:Testosterone ratio: Highest
- Characterized by peak estradiol and beginning progesterone rise
Luteal Phase
- Estradiol:Progesterone ratio: Low (progesterone dominant)
- Estradiol:Testosterone ratio: Moderate
- Characterized by high progesterone and moderate estradiol
Clinical Implications and Considerations
Timing of Measurements: Hormone levels should be interpreted in the context of cycle phase. For accurate assessment of ovarian reserve, FSH should be measured between days 2-4 of the cycle 6.
Measurement Methods: LC-MS/MS methods provide more accurate measurements than immunoassays, which have historically overestimated hormone levels, particularly testosterone in women 2.
Physiological Effects: The fluctuations in these hormones have significant effects on metabolism, fluid retention, and other physiological processes 7.
Hormone Binding: Sex hormone-binding globulin (SHBG) levels (reference range: 18-86 nmol/L) affect the bioavailability of these hormones and should be considered when interpreting total hormone levels 4.
Age-Related Changes: Testosterone exhibits an age-related decline in premenopausal women, while SHBG remains relatively stable across age ranges 4.
Measurement Challenges: Due to the pulsatile nature of hormone release, particularly LH, the timing of blood sampling is crucial for proper characterization 6.
Common Pitfalls: Failure to consider cycle phase when interpreting hormone levels can lead to misdiagnosis. Similarly, using outdated reference ranges based on less accurate immunoassay methods may result in inappropriate clinical decisions.
By understanding these normal patterns and ratios, clinicians can better interpret hormone test results and identify abnormalities that may impact women's health and quality of life.