Is checking estrogen, Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), progestin, and Thyroid-Stimulating Hormone (TSH) levels a reasonable approach for investigating female hormonal imbalances?

Hormonal Testing for Female Reproductive Dysfunction

Yes, checking FSH, LH, estradiol (not just "estrogen"), progesterone (not "progestin"), and TSH is a reasonable and guideline-supported approach for investigating female hormonal imbalances, but the timing and interpretation of these tests is critical for accurate diagnosis. 1

Core Hormone Panel and Timing

Early Follicular Phase Testing (Days 3-6)

• FSH and LH should be measured between cycle days 3-6, with the most accurate assessment calculated as the average of three blood draws taken 20 minutes apart 1, 2
• This timing captures baseline gonadotropin levels before follicular recruitment begins 2
• Abnormal FSH/LH patterns to identify:
  • LH/FSH ratio >2 suggests polycystic ovary syndrome (PCOS) and likely anovulation 1, 2
  • FSH >35 IU/L and LH >11 IU/L indicate ovarian failure 1
  • LH <7 IU/mL may indicate hypothalamic dysfunction 1

Mid-Luteal Phase Testing (Day 21 or 7 Days Post-Ovulation)

• Progesterone measurement during mid-luteal phase is the most reliable hormonal indicator of ovulation 1, 2
• Progesterone <6 nmol/L indicates anovulation 1, 2
• Common causes of anovulation include PCOS, hypothalamic amenorrhea, and hyperprolactinemia 1

Additional Hormones to Measure

• Estradiol (not generic "estrogen") should be measured on days 3-6 alongside FSH/LH 1
• TSH is essential as thyroid dysfunction commonly causes menstrual irregularity and must be excluded 1
• Prolactin should be measured in morning resting samples (not post-ictal), with levels >20 μg/L being abnormal 1

Clinical Context Matters

When These Tests Are Most Useful

The hormone panel is indicated for women presenting with: 1

• Menstrual irregularity (cycles <23 days or >35 days, or amenorrhea >6 months)
• Infertility (inability to conceive after 12 months of unprotected intercourse)
• Hirsutism or signs of androgen excess
• Galactorrhea
• Failure to initiate or progress through puberty

Distinguishing Between Conditions

For PCOS versus functional hypothalamic amenorrhea (FHA): 1

• PCOS typically shows LH/FSH ratio >2, elevated LH throughout the cycle, and normal to high estradiol 1
• FHA shows low gonadotropins (especially LH), LH/FSH ratio <1 in approximately 82% of cases, and low estradiol with thin endometrium 1
• The presence of typical FHA causes (excessive exercise, underweight, caloric deficiency, stress) combined with low endometrial thickness strongly suggests FHA over PCOS 1

Critical Pitfalls to Avoid

Timing Errors

• FSH levels fluctuate dramatically during the menopausal transition, rising to postmenopausal ranges and then falling back to normal fertile ranges within the same cycle 3, 4
• A single elevated FSH does not reliably diagnose ovarian insufficiency in perimenopausal women, as ovulation can occur after postmenopausal FSH levels are observed 3
• Measurements taken at the wrong cycle phase render results uninterpretable 1, 2

Medication Interference

• Hormonal contraceptives suppress normal FSH and LH patterns and should be discontinued at least 2 months before testing if assessing baseline reproductive function 2
• Antiepileptic drugs (particularly valproate) can impact hormone levels and cause reproductive endocrine disorders 1

Interpretation Challenges

• Normal estradiol and progesterone secretion can occur despite grossly abnormal FSH/LH patterns, which may be causally related to infertility 5
• Some women show persistently elevated LH relative to FSH without the typical midcycle surge pattern, masking ovulatory dysfunction 5

For Irregular or Absent Cycles

• Women with irregular cycles may benefit from anti-Müllerian hormone (AMH) testing, which does not vary by menstrual day and is not affected by exogenous estrogen or progesterone 2
• However, AMH interpretation requires caution in women under age 25 due to significant fluctuations 1

When to Refer

Endocrinology and/or gynecology consultation is warranted for: 1

• Prepubertal females with no signs of puberty by age 13 years with elevated FSH
• Primary amenorrhea by age 16 years despite other evidence of puberty
• Postpubertal females with menstrual cycle dysfunction suggestive of premature ovarian insufficiency
• Any patient diagnosed with ovarian insufficiency requiring sex steroid replacement therapy consideration