What is the recommended work‑up and initial management for a 30‑year‑old presenting with symptoms of hormonal imbalance such as menstrual irregularities, unexplained weight change, fatigue, altered libido, mood swings, or skin changes?

Workup and Management of Hormonal Imbalance in a 30-Year-Old

Begin with a pregnancy test, then measure morning TSH, free T4, prolactin, FSH, LH, and total testosterone to identify the most common reversible causes—pregnancy, thyroid dysfunction, hyperprolactinemia, and polycystic ovary syndrome. 1

Initial Laboratory Panel

Obtain the following tests, with FSH, LH, and testosterone drawn between cycle days 3-6 (or any time if amenorrheic):

• Pregnancy test – mandatory first step to exclude pregnancy as the cause 1
• TSH and free T4 – thyroid dysfunction (both hypo- and hyperthyroidism) disrupts menstrual cycles and is readily treatable 2, 1
• Prolactin – draw as a morning resting sample; levels >20 μg/L indicate hyperprolactinemia 1, 3
• FSH and LH – measure on days 3-6; an LH/FSH ratio >2 suggests PCOS 1
• Total testosterone – levels >2.5 nmol/L support PCOS or medication effect (e.g., valproate) 1
• Estradiol – levels <30 pg/mL confirm hypoestrogenism seen in functional hypothalamic amenorrhea 1

Clinical Assessment Details

Document specific features that guide diagnosis:

• Menstrual pattern – cycle length >35 days defines oligomenorrhea; cessation for 3 months (if previously regular) or 6 months (if irregular) defines secondary amenorrhea 1
• Weight and eating patterns – BMI <18.5 kg/m² suggests functional hypothalamic amenorrhea; BMI >25 kg/m² is associated with PCOS 1
• Exercise habits – excessive exercise in thin or athletic patients raises concern for Female Athlete Triad 1
• Hyperandrogenic signs – hirsutism (Ferriman-Gallwey score), acne, androgenetic alopecia, or truncal obesity (waist-to-hip ratio >0.9) warrant androgen testing 1
• Galactorrhea – mandates prolactin measurement and pituitary evaluation 2, 1
• Medication review – antipsychotics, antiepileptics, and hormonal contraceptives can cause menstrual irregularities 1

Interpretation Algorithm

If TSH is abnormal:

• Elevated TSH – primary hypothyroidism causes 43% of hyperprolactinemia cases in frank hypothyroidism and 36% in subclinical disease 3
• Treat hypothyroidism first; this alone may normalize prolactin and restore menses 3
• Recheck prolactin after thyroid replacement is optimized 3

If prolactin is elevated (>20 μg/L):

• Repeat as morning resting sample to exclude stress-related elevation 3
• Never draw prolactin immediately after seizure, stress, breast examination, or sexual activity – wait at least 24 hours 1
• If persistently elevated, order pituitary MRI to exclude prolactinoma 3
• Levels >100 μg/L or any elevation with headaches/visual changes require endocrine or neurosurgical referral 1

If LH/FSH ratio >2 with normal/elevated testosterone:

• PCOS is likely – confirm with mid-luteal progesterone <6 nmol/L indicating anovulation 1, 3
• Add androstenedione and DHEA-S if hyperandrogenic signs are present 1
• DHEA-S thresholds: age 20-29 >3800 ng/mL; age 30-39 >2700 ng/mL suggest adrenal pathology 1
• Androstenedione >10.0 nmol/L warrants imaging for adrenal or ovarian tumor 1

If FSH is elevated (>40 mIU/mL):

• Primary ovarian insufficiency – confirm with repeat FSH 4 weeks later (two elevated values required) 1
• Order karyotype if age <40 years to detect Turner syndrome 1

If LH/FSH ratio <1 with low estradiol (<30 pg/mL):

• Functional hypothalamic amenorrhea – assess for disordered eating, excessive exercise, or low body weight 1
• Thin endometrium (<5 mm on ultrasound) supports this diagnosis 1

Imaging Studies

• Pelvic ultrasound – indicated when hormonal tests or clinical features suggest ovarian pathology 1
• Assess endometrial thickness: <5 mm suggests estrogen deficiency; >8 mm suggests chronic anovulation with unopposed estrogen 1
• Pituitary MRI – required for persistent hyperprolactinemia or multiple pituitary hormone deficiencies 2, 3

Common Pitfalls

• Do not assume amenorrhea equals menopause in a 30-year-old; premature ovarian insufficiency can maintain unpredictable ovarian function 1
• Avoid misdiagnosing functional hypothalamic amenorrhea with polycystic ovarian morphology as PCOS – FHA patients have low LH, low estradiol, thin endometrium, and LH/FSH ratio <1 despite ovarian appearance 1
• Start corticosteroids before thyroid hormone if both adrenal insufficiency and hypothyroidism are present to avoid precipitating adrenal crisis 2
• Do not perform pelvic examination, Pap smear, clinical breast examination, or routine metabolic panels in the initial workup unless specific indications exist 1

Initial Management Based on Diagnosis

Primary hypothyroidism:

• Start levothyroxine; monitor TSH at 6-8 weeks after dosage changes 4
• Recheck prolactin after thyroid normalization 3

PCOS:

• Address metabolic factors including weight management and insulin resistance 3
• Consider metformin if insulin resistance is present 3
• Use hormonal contraceptives for cycle regulation if pregnancy not desired 3

Hyperprolactinemia (after excluding hypothyroidism):

• Refer to endocrinology for dopamine agonist therapy 3
• Obtain pituitary MRI before treatment 3

Functional hypothalamic amenorrhea:

• Address underlying causes: restore healthy weight, reduce excessive exercise, treat eating disorders 1
• Refer for bone density assessment via DXA if energy deficiency-related amenorrhea is present 1

Primary ovarian insufficiency:

• Refer to endocrinology and reproductive endocrinology 1
• Counsel that unpredictable ovarian function may persist 1