What does low FSH, LH, and Estradiol indicate in a 43-year-old on medication?

Hypogonadotropic Hypogonadism (Central/Secondary Hypogonadism)

These laboratory values—FSH 2.8 IU/L, LH 1.3 IU/L, and estradiol <40 pg/mL—indicate hypogonadotropic hypogonadism (central/secondary hypogonadism), where the pituitary gland is failing to produce adequate gonadotropins despite low estrogen levels. 1

Clinical Significance

This hormonal pattern represents a failure of the hypothalamic-pituitary-ovarian axis at the central level. In a 43-year-old woman, this is not consistent with normal perimenopause (which would show elevated FSH >35 IU/L and elevated LH >11 IU/L) 2. The inappropriately low gonadotropins in the setting of low estradiol indicate the pituitary is not responding appropriately to the low estrogen state 2, 1.

Immediate Diagnostic Workup Required

Essential Laboratory Tests

• Measure serum prolactin levels immediately to rule out hyperprolactinemia, which is a common cause of central hypogonadism and can suppress LH/FSH secretion 2, 1
• Repeat morning measurements of LH, FSH, and estradiol to confirm these findings, as transient fluctuations can occur 1
• Check TSH and free T4 to exclude central hypothyroidism, which commonly coexists with central hypogonadism 2
• Measure morning cortisol and ACTH to evaluate for concurrent adrenal insufficiency, as multiple pituitary hormone deficiencies often occur together 2

Critical Imaging

If prolactin is elevated (>20 μg/L) or if multiple pituitary hormone deficiencies are present, obtain MRI of the brain with pituitary/sellar cuts to rule out pituitary adenomas (prolactinomas or non-secreting adenomas), infiltrative disease, or other structural lesions 2, 1. This is essential because structural pituitary pathology requires specific management.

Differential Diagnosis to Consider

Medication-Induced Causes

• GnRH analogs, corticosteroids, and certain antiepileptic drugs can suppress gonadotropin secretion 1
• Oral contraceptives completely suppress FSH and LH production, with typical values showing no LH peaks and suppressed gonadotropin levels 3
• Review all current medications for potential gonadotropin-suppressing effects

Hypothalamic Amenorrhea

• Assess for excessive exercise, eating disorders, significant weight loss, or chronic stress, which can cause functional hypothalamic suppression 1
• This condition affects approximately 12% of women with certain neurological conditions but only 1.5% of the general population 1

Pituitary/Hypothalamic Pathology

• Pituitary tumors (prolactinomas or non-functioning adenomas) 2
• Hypophysitis (inflammation of the pituitary), particularly in patients with history of immune checkpoint inhibitor therapy 2
• Cranial irradiation history (doses ≥18-24 Gy can impair gonadotropin secretion) 2

Clinical Assessment

Evaluate for symptoms of hypogonadism:

• Menstrual irregularities: oligomenorrhea (cycles >35 days) or amenorrhea (no bleeding >6 months) 1
• Hypoestrogenic symptoms: hot flashes, night sweats, vaginal dryness 2
• Reduced libido, fatigue, depression, poor concentration 1
• Reduced energy and endurance 1

Management Strategy

If Prolactin is Elevated

• Repeat prolactin measurement to confirm elevation is not spurious 2
• Refer to endocrinology immediately for evaluation of prolactinoma or other pituitary pathology 2, 1
• Pituitary MRI is mandatory for persistently elevated prolactin 2

If Prolactin is Normal

• Endocrinology referral is still warranted for comprehensive evaluation of central hypogonadism 1
• Hormone replacement therapy with estrogen and progesterone should be initiated to prevent complications including bone density loss 2, 1
• Estrogen can be replaced with oral, micronized, or transdermal preparations; progesterone therapy is needed to maintain endometrial health 2

For Fertility Concerns

• Gonadotropin therapy may be indicated for women desiring pregnancy, as this can stimulate ovarian function despite central hypogonadism 1

Bone Health Monitoring

• Bone mineral density testing should be performed if chronic hypogonadism is confirmed, as prolonged hypoestrogenism leads to accelerated bone loss 2, 1

Common Pitfalls to Avoid

• Do not assume this is normal perimenopause based on age alone—perimenopause shows elevated, not low, gonadotropins 4
• Do not delay pituitary imaging if prolactin is elevated or if there are signs of multiple pituitary hormone deficiencies 2
• Low LH alone is not diagnostic—interpretation must be made in the context of other hormonal parameters and clinical presentation 1
• Always start corticosteroids before thyroid hormone replacement if both deficiencies are present, to prevent precipitating adrenal crisis 2
• Weight and obesity can influence hormone levels through increased aromatization, but this pattern still requires full evaluation 2, 1