What does low follicle‑stimulating hormone (FSH), low luteinizing hormone (LH), and mild hyperprolactinemia indicate in an 18‑year‑old woman with amenorrhea?

Hypogonadotropic Hypogonadism with Mild Hyperprolactinemia

These laboratory values indicate hypogonadotropic hypogonadism (central/hypothalamic amenorrhea) with mild hyperprolactinemia, requiring immediate evaluation to exclude a pituitary adenoma and assessment for functional hypothalamic amenorrhea (FHA) causes including eating disorders, excessive exercise, or stress. 1

Interpretation of Laboratory Values

Gonadotropin Pattern Analysis

• Low-normal FSH (4.7 IU/L) and low LH (2.2 IU/L) indicate impaired hypothalamic-pituitary secretion rather than ovarian failure 1
• This pattern is characteristic of central hypogonadism, where the hypothalamus fails to adequately stimulate the pituitary gland 1
• In primary ovarian failure, FSH and LH would be markedly elevated (typically FSH >40 IU/L), which is not present here 1, 2

Prolactin Elevation Significance

• Prolactin of 29.6 ng/mL represents mild hyperprolactinemia (normal upper limit typically 20-25 ng/mL) 3, 4
• Hyperprolactinemia inhibits the pituitary's midcycle LH surge and suppresses gonadotropin secretion, contributing to amenorrhea 5, 6
• Repeat prolactin measurement is mandatory using 2-3 samples at 20-60 minute intervals via indwelling cannula to exclude stress-related spurious elevation 7
• Persistently elevated prolactin levels warrant pituitary MRI to exclude prolactinoma, even with mild elevation 1, 4

Differential Diagnosis Priority

Primary Considerations

1. Functional Hypothalamic Amenorrhea (FHA) - Most likely diagnosis 1, 2

• Evaluate for eating disorders, preoccupation with weight, or restrictive eating patterns 1, 3
• Assess exercise volume and intensity (>6 hours/week of vigorous exercise increases risk) 1
• Screen for psychological stress, recent weight loss, or low BMI 3, 2
• FHA patients characteristically have low-normal FSH and LH with mild hyperprolactinemia 1

2. Hyperprolactinemia (Prolactinoma or Functional) 4, 6

• Obtain pituitary MRI if repeat prolactin remains elevated to exclude microadenoma or macroadenoma 1, 4
• Assess for galactorrhea by history and physical examination (present in 32-69% of hyperprolactinemic amenorrhea) 3, 4
• Check for visual field defects or headaches suggesting mass effect 4

3. Polycystic Ovary Syndrome (PCOS) with Hypothalamic Suppression - Less likely but possible 1, 7

• The low LH argues against typical PCOS (which usually shows LH/FSH ratio >2) 7
• However, PCOS can present with hypothalamic suppression in the context of severe caloric restriction or excessive exercise, masking the typical elevated LH pattern 1
• Measure total testosterone and free testosterone using LC-MS/MS to assess for biochemical hyperandrogenism 7
• Consider pelvic ultrasound to evaluate for polycystic ovarian morphology (≥20 follicles per ovary or ovarian volume ≥10 mL) 7

Essential Additional Workup

Mandatory Laboratory Tests

• TSH to exclude thyroid dysfunction as a cause of amenorrhea and hyperprolactinemia 1, 7, 3, 2
• Repeat prolactin (2-3 samples, morning fasting, at rest) to confirm elevation 7
• Total and free testosterone (preferably by LC-MS/MS) to assess for hyperandrogenism 7
• Estradiol level to assess degree of hypoestrogenism and guide treatment 1, 3
• Pregnancy test (mandatory in all amenorrhea cases, even with low gonadotropins) 3, 2

Imaging Studies

• Pituitary MRI if prolactin remains elevated on repeat testing (>25-30 ng/mL) 1, 4
• Transvaginal ultrasound to evaluate for polycystic ovarian morphology if clinical hyperandrogenism present 7

Clinical Assessment

• Detailed menstrual history: age at menarche, pattern of cycles, duration of amenorrhea 2
• Weight history: current BMI, recent weight changes, lowest adult weight 1, 3
• Exercise patterns: type, frequency, duration, and intensity 1
• Nutritional assessment: dietary intake, restrictive eating, purging behaviors 1, 3
• Stress evaluation: psychological stressors, anxiety, depression 3, 2
• Physical examination: signs of androgen excess (hirsutism, acne), galactorrhea, visual fields, signs of eating disorder 7, 3, 4

Management Approach

Immediate Actions

• Refer to endocrinology for persistently abnormal hormone levels and amenorrhea evaluation 1
• Order pituitary MRI if repeat prolactin confirms elevation 1, 4
• Assess bone mineral density (DEXA scan) given hypoestrogenic state and amenorrhea 1

Treatment Considerations Based on Etiology

If Functional Hypothalamic Amenorrhea confirmed:

• Address underlying cause: nutritional rehabilitation, reduce excessive exercise, stress management 1, 3
• Estrogen-progesterone hormone replacement therapy to prevent bone loss and maintain endometrial health 1
• Calcium and vitamin D supplementation for bone health 3
• Psychological support and eating disorder treatment if indicated 1, 2

If Hyperprolactinemia from prolactinoma:

• Dopamine agonist therapy (bromocriptine or cabergoline) to normalize prolactin and restore ovulation 4
• Surgical intervention for macroadenomas with mass effect 4

If PCOS with hypothalamic suppression:

• Address lifestyle factors (weight, exercise, nutrition) first 1
• Combined oral contraceptives for cycle regulation and endometrial protection 7
• Metformin if insulin resistance present 7

Critical Pitfalls to Avoid

• Do not assume ovarian failure based on amenorrhea alone; the low FSH excludes primary ovarian insufficiency 1, 2
• Do not dismiss mild prolactin elevation; even levels of 30-40 ng/mL can suppress gonadotropins and warrant imaging 4, 6
• Do not overlook eating disorders in young women with amenorrhea, as they are a leading cause of FHA 1, 3
• Do not delay bone density assessment; hypoestrogenic amenorrhea causes rapid bone loss requiring intervention 1, 3
• Do not assume infertility; ovulation can occur unpredictably, and contraception counseling is needed if pregnancy not desired 1