Failure to menstruate by the age of 16 is referred to as ‘primary amenorrhoea’. The likely cause of primary amenorrhoea depends on whether secondary sexual characteristics are present or not. If secondary sexual characteristics are absent, then the cause is most likely delayed puberty (see p. 45). If pubertal development is normal, then an anatomical cause should be suspected. The main ‘anatomical’ causes are:

congenital absence of the uterus; this is due to a failure of the Müllerian ducts to develop

imperforate hymen; the menstrual blood is retained within the vagina (a haematocolpos) causing cyclical lower abdominal pain each month at the time of menstruation (cryptomenorrhoea). Inspection of the vulva reveals a distended hymenal membrane through which dark blood may be seen and treatment by incision, usually under anaesthesia, is all that is required (Fig. 8.1).

Fig. 8.1Imperforate hymen (A) before and (B) after incision.

Failure to menstruate may also be physiological delay, in other words, the development is normal but there is an inherent delay in the onset of menstruation. There is often a family history of the same delay in the mother. A progestogen challenge test is useful to identify constitutional menstrual delay. A progestogen (e.g. norethisterone) is given orally for 5 days, and withdrawal should lead to a vaginal bleed. If such a bleed occurs, it is reasonable to offer reassurance that spontaneous menstruation is likely to occur. An abdominal ultrasound may be reassuring to confirm that the uterus and ovaries are normal.

Low body weight and excessive exercise are also associated with primary amenorrhoea. The other causes listed in Table 8.1 are rare, although a few are outlined under the ‘secondary amenorrhoea’, discussion below (see also Chapters 5 and 6).

Table 8.1

Causes of primary amenorrhoea

System	Problem	Incidence
Chromosomal	XO – Turner syndrome	Rare
	46,XY DSD	Rare
	Ovotesticular DSD	Rare
Hypothalamic	Physiological delay	Common
	Weight loss/anorexia/heavy exercise	Common
	Isolated GnRH deficiency	Rare
	Congenital CNS defects	Rare
	Intracranial tumours	Rare
Pituitary	Partial/total hypopituitarism	Rare
	Hyperprolactinaemia	Rare
	Pituitary adenoma	Rare
	Empty sella syndrome	Rare
	Trauma/surgery	Rare
Ovarian	True agenesis	Rare
	Premature ovarian failure	Rare
	Radiation/chemotherapy/autoimmune	Rare
	Polycystic ovaries	Common
	Virilizing ovarian tumours	Rare
Other endocrine	Primary hypothyroidism	Rare
	Adrenal hyperplasia	Rare
	Adrenal tumour	Rare
Uterine/vaginal	Imperforate hymen	Not uncommon
	Uterovaginal agenesis	Rare

Secondary amenorrhoea

Secondary amenorrhoea means the cessation of established menstruation. It is defined as no menstruation for 6 months in the absence of pregnancy. A full list of causes is given in Table 8.2, but the commonest are weight loss, polycystic ovary syndrome (PCOS) and hyperprolactinaemia. The more common conditions are discussed below.

Table 8.2

Causes of secondary amenorrhoea

System	Problem	Incidence
Physiological	Pregnancy	Common
	Lactation	Common
	Menopause	Common
Hypothalamic	Weight loss/anorexia	Common
	Heavy exercise	Common
	Stress	Common
Pituitary	Hyperprolactinaemia	Not uncommon
	Partial/total hypopituitarism	Rare
	Trauma/surgery	Rare
Ovarian	Polycystic ovary syndrome	Common
	Premature ovarian failure	Uncommon
	Surgery/radiotherapy/chemotherapy	Uncommon
	Resistant ovary syndrome	Rare
	Virilizing ovarian tumours	Rare
Other endocrine	Primary hypothyroidism	Rare
	Adrenal hyperplasia	Rare
	Adrenal tumour	Rare
Uterine/vaginal	Surgery – hysterectomy	Common
	Endometrial ablation	Common
	Progestogen intrauterine device	Common
	Asherman syndrome	Rare