The most common underlying cause of primary amenorrhea in adolescent females is hormonal or anatomical abnormalities.

- Primary amenorrhea is defined as the absence of menarche by the age of 15 in girls who have normal secondary sexual characteristics or by age 13 in those without secondary sexual development.
- The evaluation of primary amenorrhea involves a detailed history, physical examination, and appropriate laboratory and imaging studies to identify the underlying cause.

- Hormonal abnormalities often involve disruptions in the hypothalamic-pituitary-ovarian axis, which can affect the production and regulation of reproductive hormones like gonadotropins and sex steroids. Examples include hypogonadotropic hypogonadism or hypergonadotropic hypogonadism due to ovarian failure.

- Anatomical abnormalities are also a frequent cause and include conditions such as Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome), imperforate hymen, transverse vaginal septum, and outflow tract obstructions, all of which prevent the normal onset of menstruation despite normal hormonal function.

- While genetic disorders such as Turner syndrome (Option 3) are important causes of primary amenorrhea, they are less common overall compared to hormonal or anatomical causes. Similarly, hypothalamic-pituitary dysfunction (Option 1) and chronic systemic illnesses (Option 4) do contribute but are not as prevalent as primary hormonal or structural abnormalities.

In summary, the most frequent etiology of primary amenorrhea in adolescents involves disruptions in hormonal regulation or structural anomalies of the reproductive tract, making Option 2 the correct choice.

Reference: Williams Textbook of Endocrinology, 14th Edition, Chapter 21 - Disorders of Puberty and Menstrual Function