What is the recommended workup for a female patient of reproductive age presenting with irregular periods?

Workup for Irregular Periods in Reproductive-Age Women

Initial Mandatory Laboratory Testing

Begin with pregnancy testing (beta-hCG), thyroid function tests (TSH, free T4), and prolactin level measurement, as these represent the most common endocrine causes of menstrual irregularity. 1, 2

• Pregnancy test (beta-hCG) is mandatory if the patient is sexually active or if clinically indicated 2
• Thyroid function tests (TSH, free T4) should be obtained, as thyroid dysfunction is a frequent cause and SHBG levels normalize with thyroid hormone normalization 1
• Prolactin level must be measured, as hyperprolactinemia is a common cause of menstrual irregularity 2

Secondary Hormonal Evaluation

After initial screening, obtain additional hormonal studies to identify specific etiologies:

• LH and FSH levels with calculation of LH/FSH ratio (>2 suggests PCOS, though less likely with elevated SHBG; >3 may indicate functional ovarian hyperandrogenism) 1, 3
• Total testosterone (>2.5 nmol/L suggests hyperandrogenism) 1
• Complete blood count to assess for anemia, particularly microcytic hypochromic anemia in patients with heavy bleeding 4, 3

Essential Clinical History Elements

Document specific menstrual pattern details rather than vague descriptions:

• Cycle length (normal reproductive age: 21-35 days; adolescents: 21-45 days), duration, and flow volume 2, 5
• Signs of androgen excess: hirsutism, acne, male-pattern hair distribution 2
• Weight changes and BMI: overweight/obesity increases odds of both irregular periods (OR 1.29) and heavy menstrual bleeding (OR 1.37) 6
• Athletic activity level and eating patterns: assess for low energy availability (<30 kcal/kg fat-free mass/day), which disrupts GnRH pulsatility and causes menstrual dysfunction 7
• Galactorrhea or nipple discharge suggesting hyperprolactinemia 2
• Personal or family history of bleeding disorders: flooding (changing pad/tampon more than hourly), clots ≥1 inch diameter, or prolonged menses warrant hematology referral 4

Physical Examination

Perform a focused pelvic examination looking for:

• Signs of hyperandrogenism (hirsutism, acne, obesity) 2, 3
• Uterine abnormalities on bimanual examination 8
• Pallor suggesting anemia 3

Imaging Studies

Obtain pelvic ultrasound (transvaginal preferred, transabdominal if not sexually active) if hormonal tests suggest ovarian pathology or to evaluate for PCOS (>10 peripheral cysts of 2-8 mm diameter). 1, 2

• Vaginal sonography combined with endometrial biopsy reliably diagnoses endometrial hyperplasia or carcinoma 8
• Sonohysterography or hysteroscopy is superior for diagnosing endometrial polyps and fibroids, which are common in women under 40 and over 40 years respectively 8
• Do not assume functional bleeding without excluding structural pathology, especially if bleeding persists beyond 3 years post-menarche 2

Special Populations

Adolescents (Within 3 Years of Menarche)

• Observation without treatment is appropriate unless bleeding is heavy, prolonged, or significantly impacts quality of life 2
• Wider cycle range (21-45 days) is normal during this period 2
• However, hormonal evaluation may reveal previously unsuspected pathology (e.g., functional ovarian hyperandrogenism) even with normal physical examination 3

Athletes

• Assess for low energy availability (RED-S/Female Athlete Triad): calculate energy intake minus exercise energy expenditure normalized to fat-free mass 7
• Low EA (<30 kcal/kg FFM/day) disrupts LH pulsatility causing oligo-amenorrhea 7
• Screen for eating disorders, inadvertent undereating, or restrictive dietary habits 7

Referral Indications

Refer to endocrinology and/or gynecology if:

• Thyroid dysfunction is confirmed requiring specialized management 1
• Hormonal workup reveals complex endocrine abnormalities 1
• Infertility is a concern (inability to conceive after 12 months of unprotected intercourse) 1
• HMB with flooding, prolonged menses, or personal/family bleeding history suggests bleeding disorder—refer to hematology 4

Common Pitfalls to Avoid

• Do not assume anovulation without excluding structural pathology, thyroid dysfunction, hyperprolactinemia, or hyperandrogenism 2, 8
• Do not rely on patient's subjective assessment of menstrual blood loss, as it does not reflect true amount 8
• Do not overlook treatable causes in perimenarcheal girls with obesity, acne, or pallor 3
• Do not skip hormonal evaluation in patients with normal physical examination, as it may reveal unsuspected pathology 3