What are the differentials for a shortened interval of menstruation, also known as polymenorrhea?

Differential Diagnosis of Shortened Menstrual Interval (Polymenorrhea)

Polymenorrhea (menstrual cycles <21-23 days) most commonly results from anovulatory cycles due to hypothalamic-pituitary-ovarian axis dysfunction, with polycystic ovary syndrome (PCOS) being the single most prevalent endocrine cause, followed by thyroid disorders, hyperprolactinemia, and functional hypothalamic amenorrhea. 1, 2

Primary Endocrine Differentials

Polycystic Ovary Syndrome (PCOS)

• PCOS affects 4-6% of women and is the most common cause of menstrual cycle irregularities, including shortened cycles. 3, 2
• Characterized by elevated androgens, irregular or absent periods, and polycystic ovarian morphology on ultrasound. 2
• Laboratory findings typically show an LH:FSH ratio >2, which strongly suggests PCOS. 2
• Look for associated hirsutism, truncal obesity (waist/hip ratio >0.9), and acne. 1

Thyroid Dysfunction

• Both hypothyroidism and hyperthyroidism disrupt the hypothalamic-pituitary-ovarian axis and can cause shortened menstrual intervals. 2
• Initial workup should include serum TSH levels. 3, 2

Hyperprolactinemia

• Accounts for approximately 20% of secondary amenorrhea cases but can also present with irregular shortened cycles. 2
• Prolactin levels >20 μg/L are considered abnormal. 1, 2
• Look for galactorrhea (crusting on nipples or expression of breast milk in non-lactating women). 1
• Rule out pituitary tumors with MRI if clinically indicated. 1, 2

Functional Hypothalamic Amenorrhea (FHA)

• Accounts for 20-35% of secondary amenorrhea cases but can present with irregular shortened cycles before progressing to amenorrhea. 3, 2
• Caused by stress, low energy availability, or excessive exercise disrupting GnRH pulsatility. 3, 2
• Critical pitfall: 40-47% of women with FHA have polycystic ovarian morphology (FHA-PCOM), which can be misdiagnosed as PCOS. 2
• This distinction is critical because FHA-PCOM requires correction of energy deficit (>30 kcal/kg fat-free mass/day) as primary treatment, not PCOS-directed therapy. 2

Anovulatory Cycles and Luteal Phase Defects

Anovulation

• Anovulatory cycles are the most common mechanism underlying polymenorrhea, resulting in irregular endometrial shedding. 1
• Mid-luteal progesterone <6 nmol/L indicates anovulation. 1
• Common causes include PCOS, FHA, and hyperprolactinemia. 2

Shortened Luteal Phase

• Inadequate corpus luteum function leads to premature menstruation. 4
• Associated with immature hypothalamic-pituitary-ovarian axis, particularly in adolescents. 4

Iatrogenic and Medication-Related Causes

Hormonal Contraceptive Misuse

• Inconsistent or incorrect use of hormonal contraceptives is a major cause of menstrual irregularities, including shortened intervals. 3
• Missing pills or extending the hormone-free interval disrupts the cycle. 3
• Unscheduled spotting or bleeding is common during the first 3-6 months of extended or continuous use. 3

Intrauterine Devices

• Copper IUDs commonly cause irregular bleeding patterns, especially in the first 3-6 months. 5
• IUD displacement or malposition can cause abnormal bleeding. 5

Systemic and Medical Conditions

Liver Disease

• Advanced liver disease causes menstrual irregularities in >25% of women through altered estrogen metabolism. 2

Coagulopathies

• Von Willebrand disease is present in up to 20% of women with heavy menstrual bleeding and can present with shortened cycles. 5
• Platelet dysfunction or thrombocytopenia should be considered. 5

Epilepsy

• Women with epilepsy have unusually high rates of reproductive endocrine disorders, including PCOS. 1, 3
• Anovulatory cycles may be associated with higher seizure frequencies. 1

Diagnostic Approach

Initial Evaluation

• First step: Obtain pregnancy test to exclude pregnancy. 3, 2, 5
• Document menstrual patterns with a chart for at least 6 months. 1, 2
• Cycles <23 days are defined as polymenorrhea. 1

Laboratory Workup

• Measure serum FSH, LH, prolactin, and TSH levels. 3, 2
• LH and FSH should be measured based on an average of three estimations taken 20 minutes apart between day 3 and 6 of the cycle. 1, 2
• Mid-luteal progesterone measurement to assess for anovulation. 1, 2

Additional Testing

• Pelvic transvaginal ultrasound if clinical features or hormonal tests raise concern about ovarian pathology. 1
• Screen for obesity (BMI >25) and truncal obesity (WHR >0.9). 1, 2
• Assess for hirsutism using Ferriman-Gallwey score. 1
• Evaluate for eating disorders, excessive exercise, and psychological stressors in suspected FHA. 2

Health Implications

• Persistent anovulatory cycles can lead to decreased bone mineral density and increased osteoporosis risk due to hypoestrogenic states. 3, 2
• Women with menstrual disorders have higher risk of developing hypertension and cardiometabolic risk factors. 2
• Reproductive endocrine disorders are associated with higher rates of infertility. 1
• Irregular menstruation is associated with metabolic syndrome, coronary heart disease, type 2 diabetes, and adverse pregnancy outcomes. 6