Menstrual patterns can indicate overall health and reflect changes in endocrine, metabolic, or other systemic functions. Primary amenorrhea, defined as the lifelong absence of menses, warrants evaluation by age 15 years or 3 years postthelarche. Secondary amenorrhea is defined as the cessation of previously regular menses for 3 months or irregular menses for 6 months. Evaluation begins with a focused medical history, including prior menstrual patterns; eating and exercise habits; psychosocial stressors; medication use; chronic illness; and neurologic, vasomotor, or hyperandrogenic symptoms. Physical examination should assess anthropometric trends and pubertal development. Routine laboratory testing includes pregnancy testing and serum estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone (thyrotropin) levels. Additional testing, including karyotyping, serum androgen evaluation, and pelvic or brain imaging, is individualized. Functional hypothalamic amenorrhea may indicate treatment for underlying disordered eating or low bone density. Patients with premature ovarian insufficiency benefit from hormone therapy until the average age of natural menopause. Addressing lifetime metabolic disease and endometrial cancer risk is necessary for patients with polyendocrine metabolic ovarian syndrome (formerly polycystic ovary syndrome).
The menstrual cycle is an indicator of hypothalamic-pituitary-ovarian axis function and overall health and can be conceptualized as a vital sign.1–3 Menstrual cycle intervals are measured from the first day of menstruation to the first day of the next cycle.3 Primary amenorrhea is the absence of menses by age 15 years or 3 years after thelarche.1,4,5 This definition prioritizes early assessment and identification of those who would benefit from hormone therapy to treat estrogen deficiency.2,6 Secondary amenorrhea is the absence of menses for 3 months if cycles were previously regular or 6 months if irregular and warrants evaluation.7 Oligomenorrhea, menstrual intervals longer than 35 days in adults or 45 days in adolescents more than 1 year after menarche, is approached similarly to amenorrhea.3,4,8,9 Absence of thelarche by age 13 years warrants evaluation.1,7,8,10
SORT: KEY RECOMMENDATIONS FOR PRACTICE
| Clinical recommendation | Evidence rating | Comments |
|---|---|---|
| Evaluation is warranted in patients who have not reached menarche by 15 years of age or 3 years after thelarche; have experienced cessation of previously regular menses for 3 months or irregular menses for 6 months; have not reached thelarche by age 13; or have oligomenorrhea.1, 3, 4, 6, 7, 9 | C | Consensus guidelines, systematic review, and meta-analysis |
| All patients with amenorrhea should receive a pregnancy test and serum estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone (thyrotropin) measurements.3, 7, 8, 12 | C | Consensus guidelines |
| Treatment of functional hypothalamic amenorrhea should aim to correct the underlying cause of low energy availability through behavior modification, nutritional repletion, and stress reduction.12, 18, 31, 35–37 | C | Consensus guidelines based on randomized controlled trials and observational studies |
| Estrogen replacement therapy should be offered for individuals with premature ovarian insufficiency until the average age of natural menopause (50–51 years) to reduce the risk of osteoporosis and fracture.13, 43–45 Note: Progestogen therapy is also recommended in individuals with a uterus |
B | Consensus guidelines, an observational study of patient-oriented outcomes, multiple randomized controlled trials of disease-oriented outcomes |
| Estrogen replacement therapy should be offered for individuals with premature ovarian insufficiency until the average age of natural menopause (50–51 years) to prevent cardiovascular disease and urogenital atrophy.13, 43, 45 | C | Consensus guidelines; systematic review and meta-analysis of disease-oriented outcomes |
| Pelvic ultrasonography is not required to establish the diagnosis of polyendocrine metabolic ovarian syndrome (formerly polycystic ovary syndrome).4, 49–51 | C | Consensus guidelines |
| Healthy eating and guideline-directed exercise should be recommended in the treatment of polyendocrine metabolic ovarian syndrome.4, 49–51, 53, 54 | B | Consensus guidelines, systematic review of randomized controlled trials |
| Combined hormonal contraceptives are first-line therapy for menstrual abnormalities, hirsutism, acne, and endometrial protection from unopposed estrogen in patients with polyendocrine metabolic ovarian syndrome.4, 49, 51 | C | Consensus guidelines |
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.
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