Investigations
1st investigations to order
pregnancy test
Test
Pregnancy must always be ruled out in amenorrhoeic females of reproductive age.
Result
negative
serum follicle-stimulating hormone (FSH) level
Test
When an elevated FSH level is detected, it should be repeated 4-6 weeks later. Re-testing FSH in approximately but not exactly 1 month may help to avoid cyclical misinterpretation.
Result
menopausal range (>40 IU/L)
serum luteinising hormone (LH) level
Test
Hypergonadotropism is a hallmark of primary ovarian failure; however, FSH is more useful as a single test than LH. In cases where LH is significantly elevated versus FSH, autoimmune oophoritis may be suspected.
Result
elevated
serum estradiol level
Test
Estradiol levels will often but not always be low, with variations being more common earlier in the disease.
Serum estradiol levels are usually undetectable (<50 picomol/L).
Result
low
anti-Müllerian hormone (AMH) level
Test
AMH falls as women approach menopause and is undetectable after menopause. Measurement may give an early warning of incipient ovarian failure.[33]
Result
low
thyroid function tests
Test
Women with POF should be screened for underlying endocrinological disorders. Thyroid dysfunction has been associated with up to 30% of cases of POF.[34]
Result
low free thyroxine, elevated thyroid-stimulating hormone if due to autoimmune hypothyroidism
serum prolactin level
Test
Hyperprolactinaemia is a common cause of secondary amenorrhoea in women of reproductive age and should be excluded.
Result
normal
transvaginal ultrasound
Test
Useful for measurement of ovarian volume, blood flow, and antral follicle count (AFC). Women with POF will have a low AFC, low perfusion, and small ovaries.
Can identify abnormal gonads in gonadal dysgenesis, which presents with primary amenorrhoea.
May also reveal intrauterine adhesions consistent with Asherman syndrome.
Result
small ovaries with minimal follicular activity
Investigations to consider
thyroid peroxidase antibody
Test
Women with POF should be screened for underlying endocrinological disorders. Thyroid dysfunction has been associated with up to 30% of cases of POF.[34]
Result
elevated in autoimmune hypothyroidism
serum fasting glucose level
Test
Women with POF should be screened for underlying endocrinological disorders such as type 1 diabetes.
Measurement of fasting insulin level has value only in a research context and is not recommended in routine clinical practice.
Result
elevated in diabetes
electrolytes, urea, creatinine
Test
Women with POF should be screened for underlying endocrinological disorders such Addison's disease. These disorders will demonstrate variable metabolic and electrolyte abnormalities (e.g., hyponatraemia in Addison's disease).
Calcium and phosphorus will help detect hypoparathyroidism (low calcium, elevated phosphorus).
Result
variable abnormalities
karyotype
Test
Chromosome testing will not reveal single gene abnormalities or chromosomal translocations. A normal 46XX karyotype is found in the majority of cases of POF.
Result
Turner syndrome (45,XO), trisomy X, Swyer syndrome (XY gonadal dysgenesis), or mosaicism
fragile X premutation
Test
The location of the fragile X gene is Xq 27.3.[5] Especially important in cases with young onset, a strong family history, or family history of cognitive delay. The number of trinucleotide repeats correlates with severity of disease.
Result
FMR-1 gene mutation
adrenocorticotropic hormone (ACTH) stimulation test
Test
Those found to have anti-adrenal antibodies should be tested for adrenal insufficiency with an ACTH stimulation test, and as many as 3% will be found to have adrenal insufficiency.[35]
Result
normal
serum adrenal antibodies
Test
Adrenal autoimmune disease (adrenal insufficiency/Addison's disease) has been rarely associated with POF. If suspected clinically, adrenal antibodies should be measured for screening, followed by an ACTH stimulation test when the screen is positive.
Result
positive in autoimmune disorders
baseline dual-energy x-ray absorptiometry scan
Test
Decreases in bone density parallel decreases in ovarian function; by the time cessation of ovarian function is confirmed, bone density may already be significantly affected. Within 18 months of diagnosis, 50% of women show significant decreases in their bone mineral density (BMD), and two-thirds of these women will have reductions so significant that they are at high risk of fractures.[18]
Result
decreased BMD is often present by the time of diagnosis of POF
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