Diagnosis and Management of Anovulation in a 27-Year-Old Woman
This patient has anovulation, as evidenced by a mid-luteal progesterone of 2 nmol/L (well below the 6 nmol/L threshold), and requires immediate workup for polycystic ovary syndrome (PCOS), functional hypothalamic amenorrhea (FHA), and hyperprolactinemia. 1, 2
Interpretation of Hormone Results
The laboratory values confirm anovulation rather than "luteal phase deficiency":
- Progesterone 2 nmol/L is diagnostic of anovulation, as levels below 6 nmol/L indicate no corpus luteum formed and no ovulation occurred 1, 2, 3
- FSH 3.3 U/L and LH 2.3 U/L are both in the low-normal follicular range 4, 5
- The LH/FSH ratio of 0.7 (less than 1) strongly argues against PCOS, which typically shows ratios greater than 2 4, 5
- Oestradiol 99 pmol/L is within follicular phase range but relatively low 4
Most Likely Diagnosis
Functional hypothalamic amenorrhea (FHA) is the most probable diagnosis given the low LH/FSH ratio (seen in approximately 82% of FHA patients), low-normal gonadotropins, and anovulation without hyperandrogenism 4, 5. FHA affects 1.5% of the general population and is caused by energy deficit, excessive exercise, or psychological stress 2.
PCOS remains possible but less likely given the LH/FSH ratio, though it affects 4-6% of women and is the most common cause of anovulation overall 1, 2.
Required Immediate Workup
Obtain the following tests to differentiate between causes:
- Morning resting serum prolactin (abnormal if >20 μg/L) to exclude hyperprolactinemia 1, 2
- Total testosterone, androstenedione, and DHEAS to assess for hyperandrogenism suggesting PCOS 1, 2
- TSH to exclude thyroid dysfunction 2
- Fasting glucose and insulin to assess insulin resistance (common in PCOS, absent in FHA) 4, 2
- Transvaginal pelvic ultrasound to evaluate for polycystic ovarian morphology and endometrial thickness 1, 2, 5
Obtain detailed history focusing on:
- Menstrual pattern over past 6 months (cycle length, regularity) 5
- Weight changes, dietary restriction, or caloric deficit (FHA triggers) 4, 2, 5
- Exercise intensity and frequency (excessive exercise causes FHA) 2, 5
- Psychological stressors (stress sensitivity in both PCOS and FHA) 4, 5
- BMI, waist-hip ratio, and signs of androgen excess (hirsutism, acne) 2
Treatment Algorithm Based on Diagnosis
If FHA is Confirmed:
- Address underlying energy deficit by increasing caloric intake and reducing exercise intensity 2
- If fertility is desired and lifestyle modifications fail, consider gonadotropin therapy after correcting hypothalamic dysfunction 5
- If fertility is not desired, hormone replacement therapy is necessary to prevent complications of chronic hypogonadism (bone loss, cardiovascular risk) 5
If PCOS is Confirmed:
- Start clomiphene citrate 50 mg daily for 5 days beginning on cycle day 5 (after progestin-induced withdrawal bleed if amenorrheic) 6
- If no ovulation after first course, increase to 100 mg daily for 5 days 6
- Do not exceed 100 mg/day for 5 days or continue beyond 3 ovulatory cycles without pregnancy 6
- Discontinue after 6 total cycles if pregnancy not achieved 6
- Time intercourse 5-10 days after completing clomiphene course when ovulation typically occurs 6
If Hyperprolactinemia is Found:
Critical Pitfalls to Avoid
- Do not diagnose "luteal phase deficiency" when progesterone is <6 nmol/L—this represents complete anovulation, not inadequate corpus luteum function 1, 2, 3
- Do not confuse isolated polycystic ovaries on ultrasound with PCOS diagnosis—PCOS requires clinical/biochemical hyperandrogenism OR ovulatory dysfunction in addition to polycystic ovarian morphology 2
- Do not assume all anovulation is PCOS—the low LH/FSH ratio in this patient makes FHA more likely 4, 5
- Do not measure progesterone at the wrong cycle phase—it must be mid-luteal (7 days before expected menses) or the result is meaningless 2, 7
- Do not overlook weight loss history in lean patients—substantial weight reduction can trigger FHA even in women with underlying PCOS 4