A 13.5 year-old female came to clinic as she and her mother were very concerned about menarche initiation. The past medical history and record reviewed showed at 11 years 4 months she was Tanner II for breast and pubic hair development, and at 12 years 8 months she was Tanner III for both. She had no known chronic health problems and during a private interview she denied any sexual activity.
The family history revealed that her mother had menarche at age 13, and also had no abnormal gynecological or obstetric problems. The patient had a younger sister who was age 10 years. Her father’s pubertal history was unknown. There was a maternal aunt with “early onset” hypothyroidism. The review of systems was negative for pelvic or abnormal pain, large changes in weight, cold/heat intolerance, constipation, headache, visual changes, or galactorrhea. She also denied any abnormal eating patterns or excessive exercise.
The pertinent physical exam showed normal vital signs with her weight and height around the 50%. She had increased her height by approximately 9 cm in the past year. She was Tanner IV for breast and pubic hair. Her external genital examination showed normal structures including an open hymenal ring.
The diagnosis of a healthy female with likely normal progression of puberty was made. She and her mother were quite anxious and wanted testing. Her pregnancy test was negative, and hormonal levels were normal for age/pubertal stage. The patient’s clinical course 3 months later showed some spreading of pubic hair. One month later her mother sent a message to the office that menses had started. By age 15 years 0 months, she had normal menstrual cycling.
Discussion
There is a wide range of normal pubertal development and “normality” is a common question that both patients and families have. Breast budding and testicular enlargement onset can be less obvious but menarche is usually more obvious and therefore families become concerned when menarche doesn’t occur at the time they expect. Delayed puberty is onset of secondary sexual characteristics occurring > 2 standard deviations from the mean for gender, which in females is age 13 for breast development and 14 years for testicular development in males. Pubertal onset range is usually 8-13 years in females and 9-14 years in males.
Primary amenorrhea is “…no period by age 14 years in the absence of growth or development of secondary sexual characteristics, or no period by age 16 regardless of the presence of normal growth and development with the appearance of secondary sex characteristics.” Primary amenorrhea initial evaluation usually includes history, physical examination, along with pregnancy testing, thyroid stimulating hormone, follicle stimulating hormone, and luteinizing hormone testing. Bone age may also be considered especially if constitutional delay is being considered. Pelvic ultrasound to determine if there is a uterus and ovaries or other anatomic abnormalities can also assist in the early evaluation. Karyotyping, testosterone levels, and imaging of the brain/pituitary/hypothalamus may also be needed as part of the evaluation. Consultation with endocrinology and/or gynecology can also be helpful for both clinicians and families.
Learning Point
The differential diagnosis of primary amenorrhea includes:
(Note: percentages do not include delayed puberty and pregnancy)
- Constitutional delay of puberty
- Pregnancy
- Anatomic outflow tract (~20% of causes)
- Imperforate hymen
- Mullerian agenesis
- Transverse vaginal septum
- Cervical agenesis
- Androgen insensitivity syndrome
- Ovarian dysfunction (~50% of causes)
- Chromosomal abnormalities
- Turner syndrome – very common cause, most common individual cause
- Fragile X variation
- Swyer’s syndrome
- Inflammatory disorders
- Chemotherapy/radiotherapy
- Polycystic ovarian syndrome
- Turner syndrome – very common cause, most common individual cause
- Chromosomal abnormalities
- Pituitary dysfunction (pituitary and hypothalamic dysfunction ~ 25% of causes)
- Pituitary tumors
- Hyperprolactinoma
- Adenomas
- Glioma
- Meningiomas
- Diabetes insipidus
- Empty sella syndrome
- Pituitary infarction
- Pituitary tumors
- Hypothalamic dysfunction
- Functional amenorrhea – very common cause
- Severe or chronic illness
- Stress
- Disordered eating
- Weight loss such as exercise
- Kallman syndrome
- Miscellaneous infiltrative or inflammatory disorders
- Brain tumor
- Cranial radiation
- Syndromes
- Functional amenorrhea – very common cause
- Other (~ 5% of causes)
- Hyperthyroidism
- Hypothyroidism
- Diabetes, uncontrolled
- Androgen use, exogenous
- Congenital adrenal hyperplasia
Questions for Further Discussion
1. What are causes of secondary amenorrhea? A review can be found here
2. Patients with Turner’s syndrome can have what types of problems? A review can be found here
3. What are potential causes of linear growth delay? A review can be found here
Related Cases
- Disease: Primary Amenorrhea | Menstruation
- Symptom/Presentation: Amenorrhea
- Specialty: General Pediatrics | Endocrinology | Obstetrics / Gynecology
- Age: Teenager
To view pediatric review articles on this topic from the past year check PubMed.
Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews. Information prescriptions for patients can be found at MedlinePlus for this topic: Menstruation
To view current news articles on this topic check Google News.
To view images related to this topic check Google Images.
To view videos related to this topic check YouTube Videos.
Heiman DL. Amenorrhea. Primary Care: Clinics in Office Practice. 2009;36(1):1-17. doi:10.1016/j.pop.2008.10.005
Kanabolo D, Rodriguez J, Waggoner D, et al. A Phenotypic Female Adolescent with Primary Amenorrhea and Dysmorphic Features. Pediatr Ann. 2019;48(12):e495-e500. doi:10.3928/19382359-20191118-02
Garg A, Vash-Margita A, Simoni MK. Abnormal Puberty and Amenorrhea: A Review. Pediatr Ann. 2025;54(9):e294-e301. doi:10.3928/19382359-20250707-03
Marsh CA, Grimstad FW. Primary amenorrhea: diagnosis and management. Obstet Gynecol Surv. 2014;69(10):603-612. doi:10.1097/OGX.0000000000000111
Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa
You must be logged in to post a comment.