What could be the cause of delayed menarche (first menstrual period) in a young female with no apparent abnormalities?

Delayed Menarche: Causes and Evaluation

The most common causes of delayed menarche in a young female with no apparent abnormalities are constitutional delay (physiologic immaturity of the hypothalamic-pituitary-ovarian axis), functional hypothalamic amenorrhea from low body weight/excessive exercise/stress, and polycystic ovary syndrome (PCOS). 1, 2

When to Evaluate

• Primary amenorrhea requires evaluation by age 15 years, or by age 13 years if no secondary sexual characteristics (breast development) are present. 1
• Girls typically begin puberty between ages 8-10 years, with most having breast development (Tanner stage 2) by age 11. 1
• Evaluation at these thresholds is essential because physiologic delay cannot be assumed without excluding pathology. 1

Most Common Causes

Functional Hypothalamic Amenorrhea (FHA)

• Accounts for 20-35% of amenorrhea cases. 1, 3
• Associated with low body weight, excessive exercise, stress, or eating disorders. 1, 2
• Results from disrupted hypothalamic-pituitary-gonadal axis with decreased LH pulsatility, leading to low estradiol and progesterone levels. 3
• Athletes, particularly gymnasts, may have intrinsically late menarche (mean age 14.3 years) due to sport-specific selection rather than training-induced delay. 4

Polycystic Ovary Syndrome (PCOS)

• One of the most common causes, affecting 8-13% of women. 1, 2
• Presents with signs of hyperandrogenism (acne, excessive facial/body hair, scalp hair thinning) and insulin resistance. 1, 2
• Should be strongly considered in adolescents with menstrual irregularities and hyperandrogenic symptoms. 2, 5
• Obesity is strongly correlated with PCOS and menstrual irregularities. 2

Constitutional Delay

• Represents physiologic immaturity of the hypothalamic-pituitary-ovarian axis. 6
• Family history of late menarche is a key indicator—maternal menarcheal age positively correlates with daughter's age of menarche. 4
• However, this diagnosis requires excluding pathology first. 1

Other Important Causes

• Hyperprolactinemia: Accounts for approximately 20% of cases, presents with galactorrhea and prolactin >20 μg/L. 1, 2
• Thyroid dysfunction: Can cause menstrual irregularities. 2, 3
• Primary ovarian insufficiency: Characterized by elevated FSH and LH levels. 3
• Poor glycemic control in type 1 diabetes: Each 1% increase in mean total glycosylated hemoglobin delays menarche by 1.3 months. 7

Diagnostic Algorithm

Step 1: Initial Assessment

• Perform pregnancy test first to exclude pregnancy. 1, 2
• Document detailed menstrual and family history, specifically asking about maternal age of menarche. 1, 4
• Assess growth patterns and pubertal development progression (breast development, pubic hair). 1
• Screen for eating patterns, exercise habits (especially intensive athletic training), stress, and disordered eating. 2, 4
• Evaluate for signs of hyperandrogenism: acne, excessive facial/body hair, scalp hair thinning. 2
• Document BMI and recent weight changes. 2
• Review medications (antiepileptics, antipsychotics, hormonal contraceptives). 2

Step 2: Laboratory Testing

• Hormonal panel (can be done any time if no cycles) should include: 1, 2
  • FSH and LH
  • Testosterone
  • Prolactin
  • TSH
• Mid-luteal progesterone level <6 nmol/L indicates anovulation. 2

Step 3: Imaging

• Pelvic ultrasound on cycle days 3-9 (or any time if no cycles) to assess ovarian morphology and endometrial thickness. 2
• PCOS criteria include >10 peripheral cysts in one plane with thickened ovarian stroma. 2

Critical Pitfalls to Avoid

• Do not assume "normal adolescent irregularity" without proper evaluation at the defined age thresholds. Menstrual irregularity in the first years after menarche may be a symptom of pathology requiring diagnosis and treatment. 5
• Do not overlook functional hypothalamic amenorrhea in athletes or those with "normal" BMI. Even moderate exercise intensity can disrupt the hypothalamic-pituitary axis. 3, 4
• Do not miss PCOS in adolescents. It is frequently the cause of menstrual disorders in this age group and requires early identification for metabolic screening. 2, 5

Long-Term Monitoring

• If amenorrhea persists >6 months, obtain DXA scan for bone density assessment due to estrogen deficiency risk. 1, 2
• For confirmed PCOS, perform annual metabolic screening including fasting glucose and lipid panel due to increased diabetes and cardiovascular risk. 1, 2
• Both early and late menarche are associated with hypertension and greater cardiovascular disease risk later in life. 1