Primary amenorrhoea: when periods have not started

Amenorrhoea means the absence of periods. Primary amenorrhoea means periods have never begun. NICE Clinical Knowledge Summaries define it as failure to establish menstruation by the expected age, which they say is variably considered to be 15 or 16 years in girls with normal secondary sexual characteristics such as breast development, or 13 or 14 years in girls with no secondary sexual characteristics. Having reached those ages without a period, or having shown no signs of puberty, is the point at which assessment is reasonable.

The NHS puts this in context: periods usually begin at around the age of 12, though some girls start earlier or later, a delay in starting periods is not usually a cause for concern, and most girls will be having regular periods by age 16 to 18. Individual puberty timing is strongly influenced by family pattern, so the ages in the guidance are thresholds for looking, not a diagnosis.

NICE Clinical Knowledge Summaries describe many possible causes, including physiological states, outflow tract obstruction, genetic and congenital conditions, disorders of the ovaries, hypothalamus or pituitary, and disorders of other endocrine glands. The more common causes of primary amenorrhoea are listed as anatomical abnormalities due to genetic or congenital conditions, functional hypothalamic amenorrhoea related to eating disorders, stress, weight loss and excessive exercise, and polycystic ovary syndrome.

Turner syndrome is an example of a genetic cause. The NHS describes it as a rare genetic condition caused by a missing or partially missing sex chromosome, in which almost everyone has underdeveloped ovaries that can affect puberty and cause infertility, and for which hormone therapy can support growth and puberty. The NHS now names polycystic ovary syndrome as polyendocrine metabolic ovarian syndrome (PMOS) and lists irregular periods or long gaps between periods among its main symptoms.

• Constitutional delay, where puberty simply starts later in a healthy person.

• Hypothalamic suppression from low energy availability, weight loss, stress or heavy training.

• Ovarian causes, including chromosomal conditions such as Turner syndrome.

• Hormone-related conditions such as polycystic ovary syndrome, thyroid disease or high prolactin.

• Anatomical causes where the outflow of blood is blocked or part of the reproductive tract has not formed.

NICE Clinical Knowledge Summaries advise a thorough history and examination to help identify the cause. In practice the history usually covers growth, breast development, weight change, exercise, diet, stress, medicines and family history, and the examination looks at growth, pubertal stage and any features of a syndrome.

Preliminary investigations that may be considered in primary care to aid diagnosis or guide referral include ultrasound, serum prolactin, thyroid-stimulating hormone, follicle-stimulating hormone and luteinising hormone, oestradiol, and total testosterone if there are features of androgen excess. A pregnancy test is considered where relevant. The results, along with the physical findings, indicate whether the problem lies in the brain signals, the ovaries or the outflow tract.

NICE Clinical Knowledge Summaries state that referral for specialist investigation, and where appropriate management of the underlying cause, is indicated for those with primary amenorrhoea. The relevant specialists include paediatric endocrinologists, adolescent gynaecologists and, in some cases, geneticists, depending on findings. Where an eating disorder is suspected, they advise prompt referral to an age-appropriate community eating disorders service.

The investigations may include a chromosome analysis or imaging of the pelvis to clarify anatomy, and are usually coordinated by a specialist team rather than ordered piecemeal. For many young people and their families, the process is more reassuring when the plan is explained at the outset, including the likely sequence of tests and when results are expected.

Treatment is aimed at the cause. Where oestrogen is low, hormone therapy supports breast development, growth and the health of the womb and bones, as the NHS describes for Turner syndrome. Where weight loss, undereating or over-exercise are driving it, recovery of nutrition and energy balance is the treatment, and periods may return without hormones. Anatomical blockages can sometimes be corrected surgically.

Bone health is a recurrent theme. Periods reflect oestrogen exposure, and long periods without it can reduce bone density, which is why the cause is looked for rather than waiting. Fertility is another common concern; the answer depends on the cause and the sources used here do not give a general rule, so it should be discussed at the specialist visit.