How should I evaluate and treat a 16-year-old female presenting with irregular menstrual cycles?

Evaluation and Management of Irregular Menses in a 16-Year-Old

In a 16-year-old with irregular menses, first rule out pregnancy, then obtain FSH, LH, TSH, and prolactin levels to differentiate between normal adolescent anovulation (which affects up to 50% of teens and typically resolves spontaneously) versus pathologic conditions requiring intervention. 1, 2

Understanding Normal Adolescent Menstrual Patterns

• Normal menstrual cycles in adolescents range from 21–45 days, which is wider than the adult range of 21–35 days. 1, 2, 3
• Approximately 50% of menstrual irregularity in adolescents is due to neuroendocrine immaturity (aluteal or short luteal phase cycles) that resolves spontaneously, while the other 50% is associated with elevated androgens. 2
• By the fourth postmenarcheal year, 90% of cycles fall within the 21–45 day range. 2
• Cycles persistently outside 21–45 days for ≥1 year warrant full evaluation for disordered hypothalamic-pituitary-gonadal function. 2, 4

Initial Clinical Assessment

History

• Document age at menarche, cycle regularity since menarche, and duration of current irregularity. 5
• Assess for weight changes >5% in the past 6 months, current BMI, eating patterns, and exercise habits (>10 hours/week of intense training warrants evaluation for Female Athlete Triad). 1, 5
• Screen specifically for restrictive eating, fear of weight gain, body image distortion, and excessive exercise—adolescents frequently minimize these behaviors. 1
• Ask about galactorrhea, headaches, visual changes, hirsutism, and acne. 5
• Document medication use, particularly antipsychotics, antiepileptics, and valproate. 5, 6

Physical Examination

• Calculate BMI: obesity (>25 kg/m²) suggests PCOS; low BMI (<18.5 kg/m²) suggests functional hypothalamic amenorrhea (FHA). 1, 5
• Assess Tanner staging for breast and pubic hair development. 1, 5
• Examine for hirsutism (Ferriman-Gallwey scoring), acne, androgenetic alopecia, and acanthosis nigricans. 5, 6
• Perform nipple expression to detect occult galactorrhea. 5
• A pelvic examination is NOT required for initial evaluation of menstrual irregularity in healthy adolescents. 5

Laboratory Evaluation

First-Line Mandatory Tests

• Urine pregnancy test (must be performed first before any other hormonal testing). 1, 5
• FSH and LH (drawn on cycle days 3–6 if cycles present, or any time if amenorrheic). 5, 6
• TSH to exclude thyroid dysfunction. 5, 6
• Prolactin (single morning resting sample; never draw post-exercise, post-stress, or within 24 hours of a seizure). 1, 5, 6

Interpretation of Initial Results

If LH/FSH ratio >2:

• Strongly suggests PCOS. 1, 5, 6
• Add total testosterone (>2.5 nmol/L supports PCOS), androstenedione, and DHEA-S. 5, 6
• Order pelvic ultrasound (transvaginal preferred) on cycle days 3–9. 6
• Do NOT use ultrasound to diagnose PCOS if gynecologic age is <8 years post-menarche, as polycystic ovarian morphology is present in 17–22% of normal adolescents. 1

If LH/FSH ratio <1:

• Seen in approximately 82% of FHA cases. 1
• Add estradiol (<30 pg/mL confirms hypoestrogenism). 1, 6
• Assess endometrial thickness via ultrasound (thin endometrium <5 mm indicates estrogen deficiency). 1, 5

If FSH >40 IU/L:

• Suggests premature ovarian insufficiency (POI). 1
• Repeat FSH in 4 weeks (two elevated values required for diagnosis). 1, 5
• Order karyotype to exclude Turner syndrome. 1, 5

If prolactin >20 µg/L:

• Check TSH first (hypothyroidism causes secondary hyperprolactinemia). 1, 5
• If prolactin >100 µg/L or any elevation with headaches/visual changes, obtain pituitary MRI and refer to endocrinology. 5, 6

Critical Red Flags Requiring Urgent Evaluation

• No breast development by age 13 years (delayed puberty requiring earlier intervention). 1
• No menarche by age 15 years (statistically uncommon and warrants full evaluation). 1, 3
• Amenorrhea >3 months (abnormal even in early gynecologic years; the 95th percentile for cycle interval is 90 days). 4
• Significant weight loss or signs of eating disorder (requires multidisciplinary eating disorder team). 1
• Galactorrhea (suggests hyperprolactinemia). 1
• Headaches or visual changes (suggests pituitary pathology). 1
• Severe hirsutism or virilization (testosterone >5 nmol/L suggests androgen-secreting tumor). 5

Management Based on Etiology

Functional Hypothalamic Amenorrhea (FHA)

• Primary therapy: increase caloric intake to >30 kcal/kg fat-free mass/day. 1
• Reduce exercise volume and intensity if excessive. 1
• Provide nutritional counseling by a sports dietitian experienced with energy availability assessment. 1
• If amenorrhea persists >6 months despite addressing energy deficits, initiate transdermal estradiol 100 µg patch twice weekly with cyclic micronized progesterone 200 mg for 12 days/month (oral contraceptives do NOT protect bone density as effectively). 1
• Obtain DXA scan for bone mineral density if amenorrhea extends beyond 6 months, regardless of age (90% of peak bone mass is attained by age 18). 1
• Recovery of menstrual function may take >6 months despite addressing energy deficits. 1

Polycystic Ovary Syndrome (PCOS)

• Combined oral contraceptives are generally first-line treatment for ongoing menstrual dysfunction. 2
• Address metabolic concerns: screen for insulin resistance with fasting glucose and insulin. 6
• Lifestyle modification for weight management if BMI >25 kg/m². 5

Premature Ovarian Insufficiency (POI)

• Immediately initiate transdermal estradiol 100 µg patch twice weekly with cyclic micronized progesterone 200 mg for 12 days/month. 1
• Continue hormone replacement therapy until at least age 50–51 years (natural menopause age). 1
• Obtain baseline DXA scan and repeat every 1–2 years. 1
• Screen for Fragile X premutation and autoimmune antibodies (21-hydroxylase, adrenal cortex, thyroid). 1
• Refer to reproductive endocrinology for fertility counseling (5–10% have intermittent ovarian activity). 1

Common Pitfalls to Avoid

• Do NOT assume all amenorrhea in athletes or stressed adolescents is benign—other pathology must be excluded even when clinical picture suggests FHA. 1
• Do NOT prescribe oral contraceptives as first-line therapy for FHA—this masks the problem without addressing the underlying energy deficit and provides false reassurance. 1
• Do NOT overlook eating disorders—adolescents frequently minimize symptoms; direct questioning about specific behaviors is necessary. 1
• Do NOT delay bone density assessment—DXA scanning is indicated if amenorrhea extends beyond 6 months. 1
• Do NOT rely on a single FSH measurement—levels fluctuate widely, particularly in perimenopause. 6
• Do NOT measure prolactin immediately after stress, breast examination, or sexual activity—obtain a morning resting sample. 5

Referral Indications

• Persistently abnormal hormone levels despite treatment. 1, 6
• Signs of pituitary pathology (headaches, visual changes, prolactin >100 µg/L). 1, 5
• Suspected eating disorder or Female Athlete Triad. 5
• Primary amenorrhea with no breast development by age 13 or no menarche by age 16. 1
• Premature ovarian insufficiency (FSH >40 IU/L in patient <40 years). 1, 6
• Severe hyperandrogenism or rapid virilization (testosterone >5 nmol/L). 5