Initial Laboratory Evaluation for Irregular Menses

Mandatory Initial Laboratory Tests

The American College of Obstetricians and Gynecologists recommends that all reproductive-age women presenting with irregular menses require a pregnancy test first, followed by measurement of TSH, prolactin, FSH, LH, and consideration of additional hormonal testing based on clinical presentation 1
A pregnancy test (urine or serum β-hCG) is mandatory regardless of reported contraceptive use or sexual activity history, as pregnancy is the most common cause of amenorrhea 1, 2
Thyroid-stimulating hormone (TSH) testing identifies thyroid dysfunction as a reversible cause, with elevated or suppressed levels indicating hypothyroidism or hyperthyroidism 1
Prolactin testing is necessary, as elevated levels (>20 μg/L) suggest hyperprolactinemia, which may indicate pituitary adenoma or medication effect 1
Follicle-stimulating hormone (FSH) testing is required, as elevated FSH (>40 mIU/mL) confirms primary ovarian insufficiency and requires repeat testing 4 weeks later for diagnosis 1
Luteinizing hormone (LH) testing is necessary, as an LH/FSH ratio >2 strongly suggests polycystic ovary syndrome (PCOS), while a ratio <1 is seen in approximately 82% of functional hypothalamic amenorrhea cases 1

FSH, LH, and testosterone should be drawn between cycle days 3-6 if the patient has any menstrual bleeding, or at any time in amenorrheic patients 1
Progesterone should be measured mid-luteal phase (approximately day 21 of a 28-day cycle) to assess ovulatory status, with levels <6 nmol/L indicating anovulation 1

When hyperandrogenism is present, total testosterone and androstenedione testing is necessary, as testosterone >2.5 nmol/L suggests PCOS or valproate use 1
When functional hypothalamic amenorrhea is suspected, estradiol testing is necessary, as low levels indicate hypoestrogenism and support the diagnosis of functional hypothalamic amenorrhea 1
Assessment for Female Athlete Triad/RED-S is necessary, including documentation of weight changes, eating patterns, exercise habits, and consideration of bone mineral density testing via DXA in those with energy deficiency-related amenorrhea 1, 3

BMI calculation is necessary, as obesity is associated with PCOS and menstrual irregularities, while low BMI suggests hypothalamic amenorrhea 1, 3
Clitoral size assessment is necessary, as width >10 mm after retracting the clitoral hood indicates elevated androgens from ovarian or adrenal pathology 4

Pelvic ultrasonography is indicated when clinical features or hormonal tests suggest ovarian pathology, with transvaginal ultrasound being more sensitive than transabdominal for identifying structural abnormalities 1
Endometrial thickness assessment via ultrasound helps differentiate conditions: thin endometrium (<5 mm) suggests estrogen deficiency, while thick endometrium (>8 mm) suggests chronic anovulation with unopposed estrogen 1

Do not assume chemotherapy-induced amenorrhea equals menopause, as hormone levels and absence of menses are unreliable indicators during tamoxifen treatment, and premenopausal estradiol levels can occur with transient chemotherapy-induced amenorrhea 1
Do not misdiagnose functional hypothalamic amenorrhea with polycystic ovarian morphology (FHA-PCOM) as PCOS, as FHA patients typically have low LH, low estradiol, thin endometrium (<5 mm), and LH/FSH ratio <1, despite ovarian appearance on ultrasound 1
Do not skip endometrial evaluation in women >35 years, as endometrial biopsy should be performed before treatment initiation to exclude hyperplasia or malignancy in this age group with irregular menses 2
Do not forget to document medication use, as antipsychotics, antiepileptics (especially valproate), and hormonal contraceptives can cause irregular menses 1