Instalab ResearchMost testosterone in the blood is bound to proteins, primarily sex hormone-binding globulin (SHBG) and albumin. Bound testosterone is like money locked away in a safe: it’s there, but you cannot use it directly. Free testosterone, on the other hand, is like cash in your pocket, ready to be spent by your cells. Researchers have long recognized that it is this free fraction that drives many of testosterone’s effects in the body.
In women, the ovaries and adrenal glands both produce testosterone, though at levels about 15–25 times lower than men. Despite being lower in absolute terms, the presence of free testosterone is essential for functions like libido, bone health, energy balance, and even body composition.
Menstrual Cycle: Research shows that free testosterone fluctuates during the menstrual cycle. In one classic study, free testosterone was highest in the follicular and mid-cycle phases, and significantly lower in the late luteal phase. This pattern suggests that free testosterone may play a role in ovulation and reproductive function.
Pregnancy: During pregnancy, total testosterone levels often rise. But free testosterone tells a different story: it actually falls. Studies in pregnant women show that while total testosterone remains similar to non-pregnant levels, free testosterone drops significantly due to increased SHBG binding. This may help explain why pregnant women often do not experience symptoms of androgen excess despite having elevated total testosterone.
Menopause: After menopause, free testosterone declines. Clinical data show that both total and free testosterone levels are lower in postmenopausal women compared to premenopausal women. Interestingly, the proportion of free testosterone relative to total testosterone (% free) does not change much. This suggests that while overall androgen activity decreases, the balance between bound and free testosterone remains relatively stable.
Polycystic Ovary Syndrome (PCOS): PCOS is one of the most common hormonal disorders in women, and free testosterone is central to its diagnosis. Women with PCOS typically show elevated free testosterone levels, which contribute to symptoms like irregular periods, excess hair growth (hirsutism), and acne. Free testosterone measurements are considered more sensitive than total testosterone for detecting androgen excess in these cases.
Hirsutism: In women with hirsutism, free testosterone levels are often elevated even when total testosterone remains within normal ranges. Studies show that free testosterone measurements are more likely to detect abnormalities compared to total testosterone or calculated indices.
Chronic Kidney Disease (CKD): Hormonal imbalances are common in CKD, and free testosterone appears linked to body composition. In a study of women with CKD, free testosterone levels were positively correlated with lean tissue mass, suggesting a role in preserving muscle even during illness.
Pregnancy Complications and Developmental Disorders: There is intriguing evidence linking neonatal free testosterone levels with outcomes like growth and neurodevelopment. Elevated free testosterone in female infants has been associated with smaller head circumference and potential ties to autism spectrum traits. While this area needs more research, it underscores the influence free testosterone may have even before birth.
While the idea of measuring free testosterone sounds straightforward, in practice it is anything but. Because only 1–3% of testosterone in the blood is free, highly sensitive methods are required.
The gold standard is equilibrium dialysis, but it is technically demanding and not widely available. Newer methods like mass spectrometry are improving accuracy, but routine clinical labs still struggle to provide consistent results.
Clinicians sometimes rely on calculated free testosterone, using equations based on total testosterone and SHBG levels. While these calculations can be useful, they are not always reliable, especially in women where levels are already low and SHBG variations are common.
Free testosterone levels in females may seem like a small detail in the hormonal landscape, but research shows they carry outsized importance. Levels shift across life stages, higher in reproductive years, lower in pregnancy and menopause, and they can reveal conditions like PCOS, hirsutism, and CKD-related muscle loss.
The challenge is measurement: getting accurate free testosterone values remains a hurdle for everyday clinical practice. Still, as methods improve, free testosterone testing may become an even more powerful tool for understanding and supporting women’s health.
