What causes irregular menstruation?

Causes of Irregular Menstruation

Irregular menstruation is primarily caused by polycystic ovary syndrome (PCOS), functional hypothalamic amenorrhea (FHA), hyperprolactinemia, thyroid dysfunction, and primary ovarian insufficiency. 1

Most Common Endocrine Causes

Polycystic Ovary Syndrome (PCOS)

• PCOS is the single most common cause of irregular menstrual cycles, affecting approximately 4-6% of women in the general population. 1
• The condition is characterized by hyperandrogenic chronic anovulation with accelerated pulsatile GnRH secretion, leading to hormonal imbalance. 1
• PCOS presents with elevated androgens (testosterone), irregular or absent periods, and polycystic ovarian morphology on ultrasound. 2, 3
• Laboratory findings typically show an LH:FSH ratio >2, which strongly suggests PCOS. 4

Functional Hypothalamic Amenorrhea (FHA)

• FHA accounts for 20-35% of secondary amenorrhea cases and is caused by functional reduction in GnRH pulsatile secretion. 1, 4
• The 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. 1, 4
• In athletes, FHA is part of the female athlete triad or Relative Energy Deficiency in Sport (RED-S). 1
• Laboratory findings show low/normal FSH and LH levels with negative progestin challenge test. 4

Hyperprolactinemia

• Hyperprolactinemia accounts for approximately 20% of secondary amenorrhea cases. 1, 4
• Causes include pituitary adenomas, medications, hypothyroidism, and chronic renal failure. 1
• Clinical features may include galactorrhea, and laboratory findings show elevated serum prolactin levels. 4

Thyroid Dysfunction

• Both hypothyroidism and hyperthyroidism can cause menstrual irregularities by affecting the hypothalamic-pituitary-ovarian axis. 1, 4
• Altered thyroid hormone levels disrupt normal reproductive hormone regulation. 1
• Laboratory evaluation should include TSH levels in all women with irregular menses. 4

Primary Ovarian Insufficiency (POI)

• POI causes irregular menstruation through premature loss of ovarian function. 1, 4
• Laboratory findings include elevated FSH and LH levels. 4

Additional Medical Conditions

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

Menstrual Disorders and Cardiovascular Risk

• Women with menstrual disorders (heavy, painful, or irregular menstruations) have a higher risk of developing hypertension and other cardiometabolic risk factors. 5
• Both early and late menarche have been associated with hypertension and greater cardiovascular disease risk. 5

Medication-Induced Causes

Hormonal Contraceptives

• Oral contraceptives frequently induce irregular bleeding patterns, especially during the first three months of use. 5
• Breakthrough bleeding and spotting are common side effects that may persist beyond the initial adjustment period. 5
• Drug interactions with rifampin, barbiturates, phenytoin, carbamazepine, and certain antibiotics can reduce contraceptive efficacy and increase breakthrough bleeding. 6

Critical Diagnostic Pitfall: FHA-PCOM vs. True PCOS

• Approximately 40-47% of women with FHA have polycystic ovarian morphology (FHA-PCOM), which can be misdiagnosed as PCOS. 4
• Key differentiating features of FHA-PCOM include: history of energy deficit or calorie restriction, low or normal BMI (lean body type), absence of hyperandrogenic symptoms (no hirsutism or hair loss), low estradiol with negative progestin challenge test, and low or low-normal LH and FSH (not elevated LH:FSH ratio). 4
• This distinction is critical because FHA-PCOM requires correction of energy deficit as primary treatment, not PCOS-directed therapy. 4

Health Consequences of Irregular Menstruation

• Decreased bone mineral density and increased risk of osteoporosis are major complications of irregular menses, particularly in hypoestrogenic states. 1, 7
• Irregular menstruation is associated with metabolic syndrome, coronary heart disease, type 2 diabetes mellitus, and increased risk of pregnancy-related hypertensive disorders. 8
• Infertility, anemia, psychological problems, and impaired quality of life are commonly associated with menstrual irregularities. 8