From the Guidelines
The workup for primary amenorrhea should begin with a thorough history and physical examination, followed by initial laboratory testing, including follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and other relevant tests as outlined in the amenorrhoea algorithm 1. The initial step in evaluating primary amenorrhea is to rule out pregnancy, which is the most common cause of amenorrhea in reproductive-age women.
- A thorough history and physical examination are crucial to identify any signs of hyperandrogenism, thyroid abnormalities, or other systemic diseases that may be contributing to the amenorrhea.
- Initial laboratory evaluation should include FSH, TSH, and other tests as recommended in the amenorrhoea algorithm, such as dehydroepiandrosterone sulfate (DHEA/S) and human chorionic gonadotropin (hCG) 1.
- If pregnancy is excluded and these initial tests are normal, anatomic evaluation with pelvic ultrasound or MRI is recommended to assess for müllerian anomalies or outflow tract obstruction.
- For patients with elevated FSH, karyotype analysis should be performed to evaluate for disorders like Turner syndrome or other chromosomal abnormalities.
- Referral or consultation with endocrinology is recommended if the diagnosing physician is not experienced with treatment of functional hypothalamic amenorrhoea or other aetiologies of amenorrhoea, as outlined in the 2014 female athlete triad coalition consensus statement 1. The timing of the workup should be initiated by age 15 in girls with no secondary sexual characteristics or by age 16 in girls with normal development but no menses, as delayed diagnosis can impact bone health, fertility, and psychological well-being.
- It is essential to follow a systematic approach, such as the one outlined in the amenorrhoea algorithm, to ensure that all potential causes of primary amenorrhea are considered and evaluated appropriately 1.
From the Research
Evaluation of Primary Amenorrhea
The evaluation of primary amenorrhea involves a thorough history and physical examination, as well as laboratory testing to narrow down the differential diagnosis 2, 3, 4, 5, 6.
- The presence or absence of sexual development should direct the evaluation 2.
- A detailed history should include menstrual onset and patterns, eating and exercise habits, presence of psychosocial stressors, body weight changes, medication use, galactorrhea, and chronic illness 4.
- The physical examination should identify anthropometric and pubertal development trends 4.
Laboratory Testing
Initial laboratory testing for primary amenorrhea includes:
- Pregnancy test 3, 4
- Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and thyroid-stimulating hormone (TSH) 3, 4
- Additional testing, such as karyotyping, serum androgen evaluation, and pelvic or brain imaging, should be individualized based on the patient's history and physical examination findings 4
Common Causes of Primary Amenorrhea
Common causes of primary amenorrhea include:
- Constitutional delay of growth and puberty 2
- Congenital outflow tract obstruction (e.g. transverse vaginal septum or imperforate hymen) 2
- Müllerian agenesis 2
- Primary ovarian insufficiency (e.g. Turner syndrome) 3, 4
- Gonadal dysgenesis 5
- Anomalies of the hypothalamic axis 5
Treatment
Treatment of primary amenorrhea is directed by the diagnosis and may involve hormone replacement therapy, contraception, or infertility services 4, 6. The primary goal of treatment is to facilitate normal sexual development and prevent complications such as osteoporosis, endometrial hyperplasia, and heart disease 2.