Initial Investigation for Amenorrhea in Women of Reproductive Age

Introduction to Hormonal Assessment

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

FSH and LH levels are crucial for differentiating between primary ovarian insufficiency and hypothalamic-pituitary dysfunction, with elevated FSH (>40 mIU/mL) indicating primary ovarian insufficiency 1, 2
Prolactin level assessment is necessary, as hyperprolactinemia accounts for approximately 20% of secondary amenorrhea cases and may indicate a pituitary adenoma requiring urgent MRI evaluation 1, 2
TSH level assessment is essential to exclude thyroid dysfunction, a reversible cause of amenorrhea, with the American Thyroid Association stating that treating thyroid dysfunction can restore normal menstrual cycles 1, 3
LH/FSH ratio >2 suggests polycystic ovary syndrome (PCOS), a common cause of secondary amenorrhea, with the American College of Obstetricians and Gynecologists recommending further evaluation 1, 2

If FSH is elevated (>40 mIU/mL), it indicates primary ovarian insufficiency, which must be confirmed with repeat FSH 4 weeks later, according to the American Society for Reproductive Medicine 1
If prolactin is elevated (>20 μg/L), an immediate pituitary MRI is necessary to rule out prolactinoma, 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, as recommended by the American College of Obstetricians and Gynecologists 1, 2
If TSH is abnormal, treat thyroid dysfunction first, as menstrual cycles typically normalize within 2-5 days of achieving adequate thyroid hormone replacement, according to the American Thyroid Association 3

Never assume amenorrhea at age 45 is simply "menopause" without evaluation, as prolonged hypoestrogenism increases risks of osteoporosis and cardiovascular disease, regardless of the underlying cause, warns the American College of Obstetricians and Gynecologists 1, 2
Do not delay hormonal assessment, as time is critical for fertility preservation options, and immediate counseling about donor oocytes or other alternatives may be necessary if primary ovarian insufficiency is confirmed 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, according to the American College of Obstetricians and Gynecologists 1

Once hormonal testing identifies the cause, management can be appropriately directed toward either fertility treatment, fertility preservation counseling, or treatment of reversible causes, with referral to reproductive endocrinology recommended to occur simultaneously with the initial workup to avoid further delays, as suggested by the American Society for Reproductive Medicine and the European Society of Human Reproduction and Embryology 1, 2, 3, 6