What is the appropriate workup and treatment for a female patient of reproductive age presenting with oligomenorrhea (infrequent menstrual periods)?

Workup for Oligomenorrhea in Reproductive-Age Women

All women presenting with oligomenorrhea require a systematic hormonal and imaging evaluation to identify the underlying cause, with pregnancy testing as the mandatory first step, followed by measurement of FSH, LH, TSH, and prolactin levels. 1

Initial Clinical Assessment

History and Physical Examination

• Document menstrual history including age of menarche, cycle regularity, and duration of irregularity 1
• Assess weight changes, eating patterns, and exercise habits to evaluate for Female Athlete Triad or disordered eating, particularly in thin or athletic patients 1
• Calculate BMI, as obesity is strongly associated with PCOS and menstrual irregularities 1
• Evaluate for galactorrhea (suggests hyperprolactinemia), hirsutism, and acne (suggests hyperandrogenism) 2, 1
• Review all medications including antipsychotics, antiepileptics, and hormonal contraceptives, which can cause menstrual irregularities 1
• Perform thyroid examination to identify enlargement or nodules 1
• Assess Tanner staging (breast and pubic hair development) 1

Mandatory Laboratory Testing

First-Line Hormonal Panel

Draw blood between cycle days 3-6 (or at any time if amenorrheic): 1

• Pregnancy test (beta-hCG) - must be performed first to exclude pregnancy 2, 1
• FSH and LH levels - to identify primary ovarian insufficiency and PCOS 1
  • LH/FSH ratio >2 strongly suggests PCOS 2, 1
  • Elevated FSH (>40 mIU/mL) indicates primary ovarian insufficiency and requires repeat testing 4 weeks later for confirmation 1
• TSH - to identify thyroid dysfunction as a reversible cause 1
• Prolactin - elevated levels (>20 μg/L) suggest hyperprolactinemia from pituitary adenoma or medication effect 1

Additional Hormonal Testing Based on Clinical Context

• Testosterone and androstenedione - when clinical signs of hyperandrogenism are present (hirsutism, acne); testosterone >2.5 nmol/L suggests PCOS or valproate use 1
• Estradiol - when functional hypothalamic amenorrhea (FHA) is suspected; low levels indicate hypoestrogenism 1
• Mid-luteal progesterone (day 21 or 7 days post-ovulation) - levels <6 nmol/L indicate anovulation, commonly seen in PCOS, hypothalamic amenorrhea, or hyperprolactinemia 1

Imaging Studies

Pelvic Ultrasonography

• Transvaginal ultrasound is more sensitive than transabdominal for identifying structural abnormalities 1
• Indicated when clinical features or hormonal tests suggest ovarian pathology 1
• Assess endometrial thickness: 1
  • Thin endometrium (<5 mm) suggests estrogen deficiency (FHA)
  • Thick endometrium (>8 mm) suggests chronic anovulation with unopposed estrogen (PCOS)
• Evaluate for polycystic ovarian morphology 2

Diagnostic Algorithm by Hormonal Pattern

Elevated FSH (>40 mIU/mL)

• Confirms primary ovarian insufficiency - requires repeat FSH 4 weeks later (two elevated values required for diagnosis) 1
• Refer to gynecology/endocrinology for sex steroid replacement therapy 2
• Karyotype testing recommended if age <40 years to identify Turner syndrome 1
• Important caveat: Patients can maintain unpredictable ovarian function and should not be presumed infertile 3

LH/FSH Ratio >2 with Normal/Elevated Estradiol

• Strongly suggests PCOS 1
• Screen for metabolic complications: glucose intolerance, dyslipidemia, and metabolic syndrome 3
• Treatment options: 2
  • Combined hormonal contraception for cycle regulation and hyperandrogenism
  • Progestin-only contraception
  • Lifestyle modification including weight loss can restore ovulation 4

Low LH, Low FSH, Low Estradiol (LH/FSH <1)

• Indicates functional hypothalamic amenorrhea (FHA) 1
• Evaluate for disordered eating and excessive exercise 1
• Screen for low bone density via DXA in those with energy deficiency-related amenorrhea 1
• Thin endometrium (<5 mm) on ultrasound supports diagnosis 1

Elevated Prolactin (>20 μg/L)

• Suggests hyperprolactinemia from pituitary adenoma or medication effect 1
• Refer to endocrinology for further evaluation and consideration of prolactin-lowering therapy 2

Normal FSH, LH, Prolactin with Elevated TSH

• Indicates thyroid dysfunction as reversible cause 1
• Treat underlying thyroid disorder 2

Common Pitfalls and Caveats

• Do not assume polycystic ovarian morphology on ultrasound equals PCOS - FHA patients can have polycystic-appearing ovaries but will have low LH, low estradiol, thin endometrium (<5 mm), and LH/FSH ratio <1 1
• Discontinue hormone replacement therapy prior to laboratory evaluation when applicable 2
• Transvaginal ultrasonography is not recommended in virgins - use transabdominal imaging instead 2
• If medical treatment fails, further investigation with hysteroscopy is indicated to diagnose focal lesions possibly missed by endometrial sampling 2
• Endometrial biopsy is preferred over dilation and curettage for diagnosing endometrial hyperplasia or cancer due to lower invasiveness, safety, and cost 2

Referral Indications

Refer to gynecology/endocrinology/reproductive medicine when: 2, 1

• Laboratory testing reveals significant abnormalities
• Concern for eating disorder or Female Athlete Triad
• Diagnosis of primary ovarian insufficiency for sex steroid replacement therapy
• Persistent anovulation after 3-6 months of conservative management
• Fertility is desired