Aetiology
Some clinicians approach the assessment of a patient with amenorrhoea based on the presence or absence of a uterus and breast development (oestrogen production).
The World Health Organization (WHO) characterises patients based upon endogenous oestrogen production, follicle-stimulating hormone levels, prolactin levels, and hypothalamic-pituitary dysfunction.[10] The WHO classification eliminates several diagnoses based on initial information. However, further work-up is still required.
The International Federation of Gynecology and Obstetrics (FIGO) has proposed the following anatomic ovulatory disorder groups: hypothalamic, pituitary, ovarian, and polycystic ovary syndrome.[11]
[Figure caption and citation for the preceding image starts]: World Health Organization classification of amenorrhoeaCreated by BMJ Knowledge Centre [Citation ends].
Functional hypothalamic amenorrhoea
Emotional stress can impair hypothalamic function, resulting in functional hypothalamic amenorrhoea, hypogonadotropic hypogonadism. Extreme athleticism, poor dietary habits or eating disorders, and mood disorders such as depression, can affect menstruation.[12][13] Rare variants in genes associated with idiopathic hypogonadotrophic hypogonadism are found in women with hypothalamic amenorrhoea, suggesting that they may contribute to susceptibility.[14]
Premature ovarian insufficiency (POI) or natural menopause
POI should always be considered in a woman of reproductive age who describes amenorrhoea, irrespective of the lack of vasomotor symptoms. Reproductive and long-term health outcomes can be further affected if not diagnosed early.[15] Differential causes such as chromosomal anomalies or autoimmune disorders should be investigated, particularly in women aged <40 years, although clear mechanisms and conclusive associations have not been identified. A family history of POI is a major risk factor for idiopathic POI, with an up to 18-fold increased risk in first-degree relatives of women with POI.[16][17]
POI can result directly from certain chemotherapeutic agents, although menses can resume, depending on age when treated and the therapy administered. It can also occur after pelvic radiotherapy.
The cause of POI remains unexplained in many patients.[18]
Endocrine dysfunction
Polycystic ovary syndrome is a common cause of secondary amenorrhoea due to ovulatory dysfunction.[9] Other endocrine disorders should be considered, such as hypothyroidism or hyperprolactinaemia.
Hypopituitarism
Panhypopituitarism, from trauma, surgery, or haemorrhage, can result in secondary amenorrhoea. Other endocrine abnormalities will also likely ensue as a result of these aetiologies.
Obstetric or surgical procedures
Reproductive outflow tract obstructions, primarily resulting from surgical manipulation, can cause secondary amenorrhoea. Intrauterine synechiae represents one of the more common examples, yet is still relatively infrequent.[19]
Chronic illness
Long-term systemic conditions may affect menses via several mechanisms including weight loss and metabolic disorders.
Medication
Various medications can result in an iatrogenic amenorrhoea, which may be the desired outcome.[1] These include exogenous steroid hormones, primarily in the form of contraception (progestin only or oestrogen/progestin compounds).[20] Others include antipsychotic medications that alter the dopaminergic pathways, affecting the gondadotropin-releasing hormone (GnRH) pulse generator.
Substance misuse
Cocaine and opioid misuse, in particular, can cause hypogonadism.
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