Low Testosterone in Women: Why It's Missed and What Your DNA Can Tell You

Testosterone is consistently framed as a male hormone. It is not. Women produce testosterone in both the ovaries and adrenal glands, and it plays a central role in energy metabolism, libido, mood regulation, muscle maintenance, bone density, and cognitive function. The difference between men and women is one of quantity, not relevance.

What makes low testosterone in women so difficult to identify is that standard blood panels — when they measure it at all — typically report total testosterone. Total testosterone includes the fraction bound to sex hormone-binding globulin (SHBG), which is biologically inactive. The fraction that actually enters cells and drives physiological effects is free testosterone, and it is almost never tested in routine clinical care.

A woman can have a "normal" total testosterone reading while her free testosterone is functionally low. Her symptoms are real. Her labs are misleading. Her doctor tells her she's fine.

The SHBG problem

SHBG is a glycoprotein produced in the liver that binds sex hormones — testosterone and oestradiol — rendering them inactive. The more SHBG you produce, the less free testosterone circulates regardless of how much total testosterone your ovaries are making.

SHBG levels are highly genetically influenced. The rs6257 and rs6259 variants in the SHBG gene account for substantial population variation in circulating SHBG. Women carrying variants associated with higher SHBG expression can have significantly reduced free testosterone even when total testosterone sits within the reference range.

SHBG production is also upregulated by oestrogen — meaning oral contraceptives reliably elevate SHBG. Women who notice persistent low libido, fatigue, and emotional blunting after starting the pill are often experiencing exactly this: pill-driven SHBG elevation reducing the free testosterone that was previously bioavailable. This effect can persist for months to years after discontinuation, and it is not an uncommon clinical picture despite being rarely explained in these terms.

The aromatase contribution

CYP19A1 encodes aromatase, the enzyme that converts testosterone into oestradiol. Elevated aromatase activity means more testosterone is being converted before it can exert androgenic effects. CYP19A1 variants associated with higher enzyme activity — particularly in adipose tissue, which also expresses aromatase — can significantly reduce effective testosterone even in women producing normal amounts.

This is one mechanism by which body composition affects hormonal balance: adipose tissue is an active aromatase site, so higher body fat correlates with higher conversion rates and lower free testosterone independently of ovarian function. But the genetic component means some women have constitutively elevated aromatase activity regardless of body fat — a clinically distinct situation requiring a different intervention.

DIM (diindolylmethane) from cruciferous vegetables modulates oestrogen metabolism and has evidence for aromatase influence. Zinc inhibits aromatase activity at the enzymatic level. For women with genetically elevated aromatase whose free testosterone is consistently low despite adequate total testosterone, these are the rational starting points — not testosterone supplementation, which increases substrate for an already overactive conversion enzyme.

Androgen receptor sensitivity

Free testosterone must bind to the androgen receptor (AR) to exert its effects. The AR CAG repeat polymorphism determines receptor transcriptional activity — shorter repeats mean higher sensitivity, longer repeats mean the receptor responds less efficiently to the same concentration. Two women with identical free testosterone levels can have substantially different androgenic effects at the tissue level based on this variable alone.

Women with longer CAG repeats need higher free testosterone to achieve the same physiological effects as women with shorter repeats. When their free testosterone is already reduced by SHBG elevation or aromatase activity, the compounded deficit becomes clinically significant — at lab values that look "normal."

The cortisol-DHEA competition

DHEA, produced by the adrenal glands, is the primary precursor to testosterone in women. Under chronic stress, the adrenal glands preferentially produce cortisol over DHEA — directly reducing the substrate available for testosterone synthesis. The NR3C1 gene encodes the glucocorticoid receptor; variants associated with heightened receptor sensitivity amplify this cortisol competition, making the testosterone suppression more pronounced under equivalent stress loads.

This is why chronic stress is such a reliable driver of low testosterone symptoms in women, and why addressing the cortisol axis is often the prerequisite to restoring androgenic function. Ashwagandha (KSM-66 extract) has among the best evidence for cortisol blunting and consequent DHEA preservation in chronically stressed adults.

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