Premature ovarian failiure may occur due to auto-immune disease or as an isolated 'premature menopause'. The diagnosis is also known as primary ovarian failure or primary gonadal failure.
A detailed history is essential in all patients, as this will affect the differential diagnoses considerably. It is also essential to determine exactly why the patient is seeking advice as premature ovarian failure may present with primary amenorrhoea, secondary amenorrhoea, osteoporosis or infertility, each requiring different mangement strategies.
Assess the timing and staging of puberty: timing of secondary hair development, breast development, menarche, and the rate of change of height.
Premature ovarian failure typically causes secondary amenorrhoea, and so other diagnoses should be considered in patients with primary amenorrhoea.
Previous successful pregnancies may help define duration of disease.
Post partum haemorrhage leading to Sheehan’s syndrome as a cause of hypopituitarism is possible if the patient was unable to breast feed and developed secondary amenorrhoea.
Amenorrhoea and breast swelling are signs of early pregnancy which may not be noticed in the oligomenorrhoeic patient.
Weight loss may indicate the development of thyrotoxicosis, coeliac disease, or diabetes which may be associated with auto-immune ovarian failure. Weight loss will also occur with hypopituitarism which also presents with secondary amenorrhoea.
Central weight gain is associated with Cushing's, and polycystic ovarian syndrome is exacerbated by weight gain, both of which can present with oligomenorrhoea.
Loss of libido occurs with any cause of hypogonadism, but may not be reported by the patient unless specifically questioned.
This often occurs with estrogen deficiency, whereas generalised heat intolerance is more suggestive of thyrotoxicosis.
Hyperprolactinaemia of any cause causes oligomenorrhoea or amenorrhoea. However, this is associated with breast swelling, tenderness and galactorrhoea in most cases, and with biochemical hypogonadotropic hypogonadism.
Thyrotoxicosis may present with seconary amenorrhoea, though other features, sweating, palpitations, tremor, weight loss or diarrhoea, are usually obvious.
Auto-immune thyroid dysfunction is also associated with premature ovarian failure, and so clinical and biochemical screening should be performed regularly.
Anorexia nervosa and very low BMI of any cause may cause secondary amenorrhoea though this is due to hypothalamic dysfunction rather than primary gonadal failure.
Soya is known to contain large amounts of phytoestrogens which may interfere with the hypothalamic-pituitary-gonadal axis. Steroids also interact with the hypothalamic-pituitary-gonadal axis and may occasionally be found in preparations thought by the patient to be 'natural' or 'herbal'.
Excessive exercise may lead to hypothalamic dysfunction with hypogonadotropic hypogonadism rather than primary gonadal failure.
Various agents associated with hypogonadism are listed below (although it is not exhaustive):
Opiates and recreational drugs, for example diamorphine, morphine sulphate, heroin, marijuana and alcohol.
Steroids, for example hydrocortisone, beclamethasone and fluticasone, interfere with the hypothalamic-pituitary axis.
Estrogens and drugs with estrogen-like activity, such as diethylstilbestrol and digoxin, and exogenous testosterone used for body building and other sports, may also affect the hypothalamic-pituitary-gonadal axis.
Phenytoin enhances estrogen synthesis, and a range of other drugs interfere with the synthesis or action of sex steroids. These include ketoconazole, metronidazole, alkylating agents, spironolactone, cimetidine, flutamide, finasteride, and etomidate, although this problem is rarely encountered in clinical practise.