Like testosterone, oestradiol circulates in three forms. Most is bound to sex hormone binding globulin and biologically unavailable. Some is loosely bound to albumin. A small fraction circulates free.
Free and albumin-bound oestradiol together are what reach your tissues. Total oestradiol, which is what most blood tests report, does not distinguish between them.
This matters when SHBG is unusual. High SHBG locks up more oestradiol, so an apparently normal total can leave less available than the number suggests. Low SHBG does the reverse.
SHBG is not fixed, and several common things move it.
Higher SHBG: oral oestrogen including the combined pill and oral HRT, thyroid overactivity, liver disease, low body weight and ageing.
Lower SHBG: insulin resistance, obesity, thyroid underactivity, and androgen excess as seen in PCOS.
The oral oestrogen point is worth noting. Oestrogen taken by mouth passes through the liver first and raises SHBG substantially, which transdermal oestrogen does not do. That is one of several reasons the route matters.
Honestly, less often than the free testosterone equivalent.
It has value in research, in interpreting results where SHBG is clearly abnormal, and in men where oestradiol is being assessed alongside testosterone.
For most women in perimenopause, it adds little. Oestradiol varies so much through a cycle and so unpredictably through the transition that neither total nor free gives a reliable picture from one sample.
This is why guidelines advise against routine hormone testing for women over forty-five with typical symptoms.
Reference ranges vary enormously by cycle phase, and comparing a result to a single range without knowing the timing is meaningless.
In premenopausal women, levels are lowest during menstruation, peak just before ovulation, and rise again in the luteal phase. Testing on days two to five gives the most comparable baseline.
After menopause, levels fall to a low and relatively stable range.
In men, oestradiol is produced mainly by aromatase converting testosterone, largely in fat tissue. Raised levels in men usually reflect body composition rather than a primary oestrogen problem.
You need total oestradiol, SHBG and albumin, all from the same blood sample. If albumin was not measured, a population average is used, which introduces some error.
Assay quality matters more for oestradiol than for testosterone. Immunoassays perform poorly at the low concentrations found in postmenopausal women and in men, where mass spectrometry is considerably more reliable.
Related reading: A woman's hormones, explained · Should you test your hormones? · How to lower oestrogen in men · The truth about HRT research
Educational only, not medical advice. Blood results should be interpreted by a clinician.