Women with POI may present with menstrual irregularity, primary or secondary amenorrhoea or subfertility. These are often, but not always, accompanied with symptoms of estrogen deficiency including vasomotor symptoms, dyspareunia, vaginal dryness, mood disturbance, fatigue and join pain.
In women presenting with such symptoms, a thorough history and examination should be carried out to look for evidence of other conditions such as polycystic ovarian syndrome or thyroid dysfunction.
Current opinion suggests that investigation should be performed after 3-4 months of oligo-amenorrhoea.
FSH/LH levels – these should be performed on day 2-5 if menstruation is still occurring. If FSH is elevated within the menopausal range (usually considered to be >30 IU/I), this should be repeated after 4-6 weeks to confirm the diagnosis.
Esstradiol levels – these will usually be low (<70 pmol/l) but may occasionally be normal due to some residual ovarian function.
Pelvic ultrasound scan – often performed as a baseline investigation to look for alternative pathology and assess antral follicle count
Thyroid function tests and prolactin – further baseline investigations to exclude alternative pathologies.
Anti-Müllerian hormone – although this is currently thought to be the most reliable method for assessing ovarian reserve, it is not routinely used in diagnosing POI. It is sometimes performed if there is diagnostic uncertainty, usually under specialist advice.
Further investigations once the diagnosis is confirmed:
DEXA – a baseline bone density scan is usually performed at diagnosis. This is particularly important if there are additional risk factors for osteoporosis.
Karyotyping and FMR1 premutation (Fragile X) testing – particularly if the women presents below the age of 30 years or if there is a family history of learning difficulties. Ideally should be offered to all women with non-iatrogenic POI. Those who carry the FMR1 premutation should be referred to a geneticist for genetic counseling.
Adrenal and thyroid peroxidase antibody testing – this should be performed in women with idiopathic POI, or those with a suspected auto-immune cause. Those with adrenal autoantibodies should be referred to an endocrinologist for testing of adrenal function. If TPO antibodies are present, yearly testing of thyroid function is usually advised.
NICE Guidelines (2015)
The current NICE guidelines recommend the following regarding diagnosis of POI:
- Take into account the woman’s clinical history (for example, previous medical or surgical treatment) and family history when diagnosing premature ovarian insufficiency.
- Diagnose premature ovarian insufficiency in women aged under 40 years based on:
- menopausal symptoms, including no or infrequent periods (taking into account whether the woman has a uterus) and
- elevated FSH levels on 2 blood samples taken 4–6 weeks apart.
- Do not diagnose premature ovarian insufficiency on the basis of a single blood test.
- Do not routinely use anti-Müllerian hormone testing to diagnose premature ovarian insufficiency.
- If there is doubt about the diagnosis of premature ovarian insufficiency, refer the woman to a specialist with expertise in menopause or reproductive medicine.