Women and Testosterone

Happy Thursday!

Let me tell you about a conversation I have over and over again.

A woman reaches out.

She's tired. Her mood is flat. Her focus is gone. Libido is nonexistent. She's read enough to know hormones are involved.

Then I ask what her testosterone levels are.

Silence.

Most women have never had them checked. A lot of providers never offer. And when they do get tested, the result gets waved off as "normal for your age" without a number ever being shared.

Testosterone is the most abundant biologically active sex steroid in a woman's body. Not estrogen, testosterone.

Circulating levels run roughly ten times higher than estradiol, even at peak reproductive years.

And production starts dropping in your late 20s. By 45, most women have lost about half of what they had at 25.

Why do I bring this up?

Because a new study in the Journal of Personalized Medicine just put real numbers on what happens when you actually replace testosterone.

Let’s look at what they found.

The Myth

Testosterone in women does heavy lifting across nearly every system that matters.

It drives energy production at the mitochondrial level.

It regulates mood by modulating dopamine and serotonin signaling.

It maintains lean muscle.

It supports hippocampal neurogenesis, which is a fancy way of saying your brain needs it to grow new memory-related neurons.

It stimulates red blood cell production.

It influences insulin sensitivity and lipid metabolism.

Estrogen and progesterone matter. I'm not arguing against them. But they cannot do what testosterone does. They operate on different receptors and different pathways.

Women who do BHRT with only estrogen and progesterone are running a hormone protocol with a missing pillar.

The Study

Researchers tracked 332 women on individualized testosterone replacement therapy.

Ages ranged from 27 to 78, with an average of 45. A subset of 120 women also got paired blood work at baseline and 12 weeks.

The protocol was simple.

Start with a blood test, administer a low physiologic dose, retest, and then adjust.

Then target the upper end of the premenopausal range, 25 to 50 ng/dL total testosterone (still too low in my opinion, but better than nothing).

Delivery options were topical cream, oral troches, or subcutaneous injections.

Women rated change across eight symptom domains.

Energy, depression, irritability, anhedonia, sexual interest, relationship satisfaction, concentration, and memory.

Every single domain improved.

Interestingly, libido was one of eight things measured, and it wasn't even the star of the show.

The real headline was what testosterone did to everything else.

Energy

84.3% of women reported improvement in energy and fatigue. That was the highest number of any domain.

When researchers asked women to pick their single biggest benefit, energy took the top spot again at 64.2%.

Mood came in second at 49.7%. Sexual desire was third at 41.3%.

Read that one more time. Energy and mood ranked above libido.

The FDA has never approved a testosterone product for women in the US.

The only sanctioned clinical use is postmenopausal low libido.

That framing has shaped how doctors think, how insurance covers it, and what women even believe they're allowed to ask for.

The data tells us that framing is way too narrow.

The hormone that gets prescribed for sex drive is actually delivering its biggest value in energy and mood.

The clinical guidelines haven't caught up.

If you're exhausted and flat and your hormones are low, testosterone might matter more than any supplement, stack, or peptide you're currently chasing.

Mood and Cognition

Depression improved in 70.8% of women. Irritability in 69%. Anhedonia, which is the clinical term for loss of pleasure, improved in 67.5%.

These are numbers that would get a psychiatric drug fast-tracked for emergency approval.

Testosterone modulates dopamine and serotonin directly.

When levels drop, mood regulation gets ugly. When levels are restored, everything cleans up.

The cognitive piece was interesting.

Memory and concentration started at the lowest scores of any domain at one month.

They didn't show meaningful improvement until the 4 to 6-month mark.

Why?

Because brain tissue takes longer to remodel than energy metabolism does.

Testosterone supports hippocampal neurogenesis and BDNF expression, but growing new neurons is not a 30-day process.

This is the reason so many women try TRT for 12 weeks, don't feel a cognitive shift, and quit.

They stopped three months before the brain benefits were going to kick in.

Biomarker Data

All five biomarkers moved in the right direction with massive effect sizes.

100% of women saw their testosterone rise.

86.7% had meaningful hemoglobin increases.

77.5% had SHBG drop.

74.2% had triglycerides come down.

Every post-treatment value stayed inside the normal physiologic range.

Cardiovascular disease is the leading cause of death for women.

Triglycerides rise through the menopausal transition. Testosterone therapy pushed them down by nearly 13% in three months.

That's the opposite of what most people assume testosterone does to women's cardiovascular risk.

Duration Matters More Than Dose

At 1 month, only 5.4% of women reported significant improvement in quality of life.

At greater than 12 months, 51.5% did. And not a single woman in the 12+ month group reported no change.

The benefits compound.

Most published trials on testosterone in women run 12 to 24 weeks. The study authors specifically called this out as a problem. These are trial windows that cut off just as the deeper benefits are starting to show.

If you start TRT, plan on six to twelve months before you judge the results. The energy shift comes fast. The mood shift comes within a couple of months.

The cognitive changes and full restoration of quality of life take longer.

Real hormone optimization is a six-month conversation at minimum.

Final Thoughts

If you're on BHRT and still feel off, ask for a testosterone panel that INCLUDES free testosterone.

Don't accept "normal for your age" as an answer without seeing a number.

A woman at 50 with the testosterone of a 50-year-old is a woman running on half of what she had at 25. That's not normal!

I favor injections, but in this study, the other delivery mechanisms worked too.

Pick what fits your lifestyle best.

Testosterone is foundational, and most women who need it have no idea they do.

Best,

Hunter Williams

Further Reading

Elggren CW, et al. Testosterone Replacement Therapy in Women Is Associated with Improved Symptom Burden and Favorable Biomarker Changes. Journal of Personalized Medicine. 2026. https://doi.org/10.3390/jpm16050231