Initial Investigation for 45-Year-Old Woman with 7-Month Amenorrhea Desiring Pregnancy
The most appropriate initial investigation is measuring LH and FSH levels (along with prolactin and TSH) to identify the underlying endocrine cause of amenorrhea, as this will determine both her current fertility potential and guide appropriate management. 1, 2
Why Hormonal Assessment is the Priority
At age 45 with 7 months of amenorrhea and fertility desires, the critical first step is determining whether she has entered premature ovarian insufficiency versus other reversible causes of amenorrhea. The American College of Obstetricians and Gynecologists recommends performing hormonal assessment, including serum FSH, LH, prolactin, and TSH levels, to identify the underlying cause of secondary amenorrhea in reproductive-age women. 1 The Endocrine Society emphasizes that endocrine dysfunction accounts for the vast majority of secondary amenorrhea cases, making hormonal evaluation the essential starting point. 1
The Complete Initial Laboratory Panel
The initial workup should include:
FSH and LH levels: These differentiate between primary ovarian insufficiency (elevated FSH >40 mIU/mL) and hypothalamic-pituitary dysfunction (low/normal FSH). 1, 2 This distinction is crucial because it determines whether she has any remaining fertility potential.
Prolactin level: Hyperprolactinemia accounts for approximately 20% of secondary amenorrhea cases and may indicate a pituitary adenoma requiring urgent MRI evaluation. 1, 2 Delaying imaging when prolactin is elevated can lead to visual field defects requiring urgent intervention. 1
TSH level: Thyroid dysfunction is a reversible cause of amenorrhea that must be excluded in all cases. 1, 3 The American Thyroid Association states this is essential because treating thyroid dysfunction can restore normal menstrual cycles. 3
LH/FSH ratio: An LH/FSH ratio >2 with normal or elevated LH suggests polycystic ovary syndrome (PCOS), one of the most common causes of secondary amenorrhea. 1, 2
Algorithmic Interpretation of Results
If FSH is elevated (>40 mIU/mL): This indicates primary ovarian insufficiency, which must be confirmed with repeat FSH 4 weeks later (two elevated values required). 1 Critically, the American Society for Reproductive Medicine notes that patients with primary ovarian insufficiency can maintain unpredictable ovarian function and should not be presumed infertile. 1, 4 However, at age 45, this significantly limits her fertility options and requires urgent referral to reproductive endocrinology.
If prolactin is elevated (>20 μg/L): Order pituitary MRI immediately to rule out prolactinoma, as this is the most common pathologic cause of hyperprolactinemia. 1, 2
If LH/FSH ratio >2: Suspect PCOS and order pelvic ultrasound to identify polycystic ovarian morphology. 1, 2 This is a treatable cause with fertility preservation options.
If TSH is abnormal: Treat thyroid dysfunction first, as menstrual cycles typically normalize within 2-5 days of achieving adequate thyroid hormone replacement. 3
Why Other Options Are Premature
Endometrial biopsy is not indicated as an initial investigation unless there are specific risk factors for endometrial pathology (such as prolonged unopposed estrogen exposure with thick endometrium >8mm on ultrasound). 1 The hormonal assessment must come first to determine the cause of amenorrhea.
Hysterosalpingogram evaluates tubal patency and is only relevant after establishing that she has ovarian function capable of producing oocytes. 5 If hormonal testing reveals primary ovarian insufficiency, HSG becomes irrelevant for natural conception planning.
Thyroid function tests alone are insufficient, as they represent only one component of the necessary hormonal panel. 1, 2
Critical Pitfalls to Avoid
Never assume amenorrhea at age 45 is simply "menopause" without evaluation. The American College of Obstetricians and Gynecologists warns that prolonged hypoestrogenism increases risks of osteoporosis and cardiovascular disease, regardless of the underlying cause. 1, 2
Do not delay hormonal assessment. At age 45, time is critical for fertility preservation options. If she has primary ovarian insufficiency, she needs immediate counseling about donor oocytes or other alternatives. 1
Assess endometrial thickness if ultrasound is performed, as thin endometrium (<5mm) suggests estrogen deficiency, while thick endometrium (>8mm) suggests chronic anovulation with unopposed estrogen, increasing endometrial cancer risk. 1
Immediate Next Steps After Hormonal Results
Once hormonal testing identifies the cause, management can be appropriately directed toward either fertility treatment (if ovarian function remains), fertility preservation counseling (if ovarian insufficiency is confirmed), or treatment of reversible causes (thyroid dysfunction, hyperprolactinemia). 1, 2, 3 Given her age and fertility desires, referral to reproductive endocrinology should occur simultaneously with the initial workup to avoid further delays. 5