What causes delayed periods?

Causes of Delayed Periods

Polycystic ovary syndrome (PCOS) is the single most common cause of delayed periods, affecting 4-6% of women in the general population, followed by functional hypothalamic amenorrhea (FHA), hyperprolactinemia, and thyroid dysfunction. 1, 2

Primary Endocrine Causes

Polycystic Ovary Syndrome (PCOS)

• PCOS accounts for the majority of irregular menstrual cycles and presents with elevated androgens, irregular or absent periods, and polycystic ovarian morphology on ultrasound. 1
• Laboratory findings typically show an LH:FSH ratio >2, which strongly suggests PCOS. 1
• The condition is characterized by hyperandrogenic chronic anovulation with accelerated pulsatile GnRH secretion. 2
• Critical pitfall: Approximately 40-47% of women with FHA have polycystic ovarian morphology (FHA-PCOM), which can be misdiagnosed as PCOS—this distinction is critical because FHA-PCOM requires correction of energy deficit as primary treatment, not PCOS-directed therapy. 1

Functional Hypothalamic Amenorrhea (FHA)

• FHA accounts for 20-35% of secondary amenorrhea cases and results from functional reduction in GnRH pulsatile secretion. 1, 2
• Main contributing factors include stress and increased stress sensitivity, vigorous exercise patterns, weight loss and low BMI, psychological disorders, and caloric restriction or energy deficit. 2
• In athletes, FHA is part of the female athlete triad or Relative Energy Deficiency in Sport (RED-S). 2
• This condition causes low estrogen levels, not excess estrogen, leading to disruptions in LH pulsatility and decreased estradiol and progesterone. 3

Hyperprolactinemia

• Accounts for approximately 20% of secondary amenorrhea cases through elevated serum prolactin levels. 1, 2
• Causes include pituitary adenomas, medications, hypothyroidism, and chronic renal failure. 2
• Prolactin levels >20 μg/L are considered abnormal, though levels may be mildly raised in patients with epilepsy. 4
• Pituitary MRI may be indicated if clinical features (galactorrhea) or laboratory results suggest hypothalamic-pituitary axis abnormality. 4

Thyroid Dysfunction

• Both hypothyroidism and hyperthyroidism cause menstrual irregularities by affecting the hypothalamic-pituitary-ovarian axis. 1, 2
• Oligomenorrhea (cycles longer than 35 days) is the most common menstrual disturbance in thyroid disorders. 5

Additional Medical Causes

Chronic Liver Disease

• Advanced liver disease causes menstrual irregularities in >25% of women through altered estrogen metabolism and disruption of the hypothalamic-pituitary axis. 1, 2

Medication-Induced Causes

• Oral contraceptives frequently induce irregular bleeding patterns, especially during the first three months of use. 1
• Delayed application or detachment of contraceptive patches for ≥48 hours can cause delayed periods and requires back-up contraception until a patch has been worn for 7 consecutive days. 4

Primary Ovarian Insufficiency

• Characterized by elevated FSH (>35 IU/L) and LH (>11 IU/L) levels. 4
• Patients can maintain unpredictable ovarian function and should not be presumed infertile. 6, 7

Diagnostic Approach

Initial Evaluation

• The first step is always a pregnancy test to exclude pregnancy. 3, 6
• Obtain menstrual chart for at least 6 months to document cycle patterns: <23 days indicates polymenorrhea, >35 days indicates oligomenorrhea, and no bleeding >6 months indicates amenorrhea. 4

Laboratory Assessment

• Initial workup should include serum FSH, LH, prolactin, and TSH levels. 6, 7
• LH, FSH should be measured based on an average of three estimations taken 20 minutes apart between day 3 and 6 of the cycle. 4
• Progesterone measurement during mid-luteal phase: levels <6 nmol/L indicate anovulation, commonly caused by PCOS, FHA, or hyperprolactinemia. 4

Additional Testing

• Pelvic ultrasonography is indicated if clinical features or hormonal tests raise concern about ovarian pathology; transvaginal ultrasound is more sensitive than transabdominal. 4
• Androgen profile should be obtained for suspected PCOS. 7
• Karyotyping may be needed for primary amenorrhea or suspected chromosomal abnormalities. 7

Clinical Red Flags and Screening

Assess for Associated Conditions

• Evaluate for eating disorders, excessive exercise, and psychological stressors in suspected FHA, as these patients are at risk for decreased bone density. 6, 7
• Screen for obesity (BMI >25) and truncal obesity (waist/hip ratio >0.9), assessing menstrual regularity in cases of cycle disturbance. 4
• Look for hirsutism (male escutcheon pattern), which may indicate hyperandrogenism requiring investigation. 4
• Check for galactorrhea (crusting on nipples, expression of breast milk in non-lactating women), which warrants prolactin measurement and exclusion of hypothyroidism. 4

Long-term Health Implications

• Decreased bone mineral density and increased risk of osteoporosis are major complications of irregular menses, particularly in hypoestrogenic states. 1, 2
• Women with menstrual disorders have higher risk of developing hypertension and other cardiometabolic risk factors. 1
• PCOS patients are at risk for glucose intolerance, dyslipidemia, and metabolic syndrome. 6