Testosterone in Women: 332-Patient Study Shows Energy, Mood Gains

Key Takeaways: A retrospective study of 332 women aged 27 to 78 on individualized testosterone therapy, published in the Journal of Personalized Medicine on April 22 and broadly covered May 7, 2026, reports 84.3% improvement in energy and fatigue, more than 65% improvement in mood domains, and 89.7% reporting better overall quality of life. All five tracked biomarkers moved favorably -- total testosterone +151.8%, free testosterone +216.7%, hemoglobin +5.5%, SHBG -13.3%, and triglycerides decreased. Cognitive gains showed a delayed trajectory at 4 to 6 months. The data is observational, not randomized, but it begins to fill a long-standing evidence gap: international guidelines have restricted approved indications to hypoactive sexual desire because that is where randomized trials existed, while women receiving testosterone in the real world consistently reported broader benefits. This study is the largest published cohort to date documenting those broader benefits with both symptom and biomarker outcomes.

What the Study Reported

On April 22, 2026, the Journal of Personalized Medicine published a retrospective observational study titled "Testosterone Replacement Therapy in Women Is Associated with Improved Symptom Burden and Favorable Biomarker Changes" [1]. Major business and consumer press coverage hit on May 7, 2026 [2] [3], pushing the findings into the women's health news cycle.

The work was conducted by Dr. Ben Bikman, PhD, and Dr. Paul Reynolds, PhD, of Brigham Young University in collaboration with a telehealth platform that prescribes individualized, biomarker-guided testosterone therapy to women. The cohort included 332 women aged 27 to 78 (mean 45.7 years) -- a population spanning premenopausal women with low testosterone, perimenopausal women, and postmenopausal women.

The methodology has both strengths and clear limits. Strength: it tracked eight pre-specified symptom domains and five objective biomarkers across a real-world treatment population, which matches how women's testosterone is actually being prescribed. Limit: it is retrospective and observational, with no placebo control. There is no direct way to separate testosterone effect from regression to the mean, expectancy effects, or self-selection of women who sought treatment because they were already responsive to it.

With those caveats stated, the magnitude of the effects is striking.

The Symptom Outcomes

Across the eight domains the researchers tracked, women reported:

• Energy and fatigue: 84.3% improved. This was the largest effect size and the symptom women themselves most often flagged as the primary benefit.
• Mood, depression, and irritability: over 65% improved in each domain.
• Anhedonia (loss of pleasure): over 65% improved.
• Sexual interest: over 65% improved.
• Cognitive domains (memory, concentration): meaningful improvement emerged at 4 to 6 months, with a slower trajectory than energy and mood.
• Quality of life: 89.7% reported improvement, with the share reporting significant improvement rising from 5.4% at one month to 51.5% beyond 12 months.

When the researchers asked women to self-identify their single greatest area of benefit, energy and fatigue led at 64.2%, mood second at 49.7%, and sexual desire third at 41.3%. This ordering is the headline finding for clinical practice: the women in the cohort were not primarily seeking or experiencing libido benefit. They were experiencing energy and mood benefit at higher rates.

The Biomarker Outcomes

All five tracked biomarkers moved in the favorable direction:

• Total testosterone: +151.8% (Cohen's d = 3.60, very large effect)
• Free testosterone: +216.7% (d = 3.01, very large)
• Hemoglobin: +5.5% (d = 2.03, large)
• SHBG: -13.3% (d = 1.57, large)
• Triglycerides: decreased (favorable cardiometabolic shift)

The hormone changes confirm the biology: testosterone levels rose from low baseline into a physiologic premenopausal range, free testosterone rose more than total (because SHBG dropped), hemoglobin rose modestly (consistent with androgen action on erythropoiesis but well within normal limits), and SHBG and triglycerides moved in the direction associated with improved metabolic health.

The very large effect sizes (d > 1.5 across the board, several above 3) make it unlikely the biomarker changes are explained by anything other than the intervention. Symptom outcomes have softer interpretation, but the biomarker leg of the study is hard to argue with.

Why This Study Matters

For two decades, testosterone therapy in women has been stuck in an awkward regulatory and evidence position. The international consensus position statement -- the most cited document in the field -- restricted recommended use to hypoactive sexual desire disorder in postmenopausal women, because that was the only indication with adequate randomized trial support [4]. The FDA has no approved testosterone product specifically designed for women, and the recent FDA guidance on a development pathway for women's testosterone is still focused on HSDD.

But the women showing up in clinics are not coming in for HSDD only. They are coming in for energy, fatigue, mood symptoms, brain fog, and a vague sense that "something is off." Experienced clinicians who treat women's hormonal symptoms have been prescribing testosterone for these broader indications based on:

1. The biological plausibility (testosterone is a neuroactive steroid with effects on serotonin, GABA, and the amygdala).
2. Real-world response patterns.
3. Smaller observational studies and pilot data.

What this 332-patient study contributes is the largest single dataset to date documenting that real-world broader-benefit pattern, with both symptom and biomarker outcomes published in a peer-reviewed journal. It does not replace randomized data, but it makes the gap between guideline language ("only for HSDD") and prescribing reality ("being used for energy, mood, cognition, libido") harder to ignore.

Where This Aligns With Other Recent Evidence

The 332-patient study does not stand alone. The recent evidence stack pointing in the same direction:

• A 2024 510-woman pilot study at a UK menopause clinic found significant improvement in nine pre-specified mood and cognitive symptoms with testosterone cream or gel.
• A recent Australian study showed that 5 mg per day of transdermal testosterone is sufficient to bring postmenopausal women into the premenopausal physiologic range -- supporting low-dose, individualized protocols.
• The recent Acrux phase 3 program for female testosterone is moving the FDA pathway forward.
• The FDA has recently removed misleading hormone therapy black box warnings, reflecting an evidence-driven re-evaluation of women's hormone treatment broadly.

Where This Does Not Settle the Argument

Two important things this study cannot do:

• It cannot establish causation. That requires a randomized placebo-controlled trial in women, with broader endpoints than HSDD. Such a trial is exactly what experienced clinicians, patient advocates, and now the FDA have been pushing toward.
• It cannot define the right dose for an arbitrary individual. The protocol used individualized, biomarker-guided titration. The lesson is not "everyone should get this dose"; the lesson is "individualized titration with monitoring works."

What the Cognitive Trajectory Tells You

The most clinically useful nuance in the study is the time-course difference between domains.

Energy and mood improved relatively early -- some women reported gains within the first month, with the share of significant improvements continuing to grow over the year. Cognitive improvements (memory, concentration, mental clarity) lagged, with meaningful gains emerging at 4 to 6 months and continuing to build through 12 months.

This matches what underlying neurobiology would predict. Energy and acute mood depend heavily on neurotransmitter availability, autonomic balance, and HPA axis tone -- systems that adjust within weeks. Cognitive function depends on slower processes: dendritic remodeling, remyelination, and integration of new neural connections. Brain plasticity runs on a multi-month timescale, not a multi-week one.

The clinical translation: if you are starting testosterone primarily for cognitive symptoms (brain fog, working memory, focus), plan for a 4-to-6-month evaluation window before judging response. If you stop at week six because "nothing happened with my memory," you are making the decision before the relevant biology has had time to operate. Energy and mood serve as earlier signals that the intervention is working, even if cognition has not yet caught up.

What "Individualized, Biomarker-Guided" Actually Means

The study's protocol is described as individualized and biomarker-guided rather than a fixed-dose regimen. This is more than a marketing phrase. The real-world version of this approach involves:

1. Baseline labs. Total testosterone, free testosterone, SHBG, estradiol, hemoglobin, full thyroid panel, lipids, fasting metabolic markers, and clinical history. Without baseline numbers there is nothing to titrate toward.
2. Starting dose calibrated to the patient. Most women start in the 4-to-6 mg per day transdermal range (cream or gel), which the recent Australian work confirms typically lands free testosterone in the upper premenopausal physiologic range. Pellet doses translate differently. Injection protocols in women are far less common and require more careful monitoring.
3. Recheck at 6 to 12 weeks. Total and free testosterone, SHBG, hemoglobin. If free testosterone is at the high end of premenopausal range and symptoms are improving, hold the dose. If free testosterone is low and symptoms are partial, raise the dose. If free testosterone is high and symptoms are partial, the issue is not dose -- look for other contributors (thyroid, sleep, iron, mood disorders).
4. Long-term monitoring. Annual labs minimum, more frequent during titration. SHBG and hemoglobin are the most useful guard rails for over-treatment.

This is the framework the 332-patient study cohort was treated under, and it is the framework experienced women's hormone clinics use. A clinic that hands out testosterone without baseline labs, or at a fixed dose without titration, is not delivering this standard of care. See Best Online HRT Clinic for Women for clinics that follow this approach.

Implications for Women Considering Testosterone

The most useful framing of the new study for women considering treatment is not "this proves testosterone works for energy and mood." That overstates what an observational cohort can prove. The accurate framing is "the largest real-world dataset to date documents the broader benefits women have been reporting, the biomarker changes confirm the biology is doing what it should, and the gap between guideline-restricted indications and how testosterone is actually being prescribed is closing."

When Testosterone Becomes a Reasonable Conversation

Common scenarios where the conversation makes clinical sense:

• Persistent energy and fatigue that started in the late 30s or 40s and is not explained by thyroid, iron, sleep apnea, or major depression.
• New-onset mood symptoms in the perimenopausal or postmenopausal window where hormonal contribution is plausible.
• Cognitive symptoms -- brain fog, word-finding difficulty, concentration loss -- in the same age window. See HRT and Brain Fog.
• Low libido with or without other symptoms (the FDA-approved evidentiary path).
• Postmenopausal women with hot flashes, sleep disruption, and mood changes who have been considering combined HRT and want to know whether adding testosterone makes sense. The testosterone-for-menopause guide walks through that decision in detail.

In all of these cases, the path forward is the same: baseline labs, evidence-based clinical evaluation, and individualized titration. Not "ask for testosterone and start a pellet."

When It Is Not the Right Answer

Testosterone is not the answer for every symptom. Real fatigue from anemia, untreated thyroid disease, sleep apnea, or major depression will not respond to testosterone -- and starting testosterone before evaluating those causes can delay correct diagnosis. Real cognitive decline from neurodegenerative disease has its own workup. Real menopausal symptoms often need estrogen and progesterone first, with testosterone added only if symptoms persist or are dominantly androgen-deficiency-pattern.

A clinic that treats every symptom with testosterone is not delivering the same level of care as one that runs a real differential diagnosis. The study's protocol included full lab evaluation precisely so that the women included were appropriate candidates.

How This Connects to Choosing a Clinic

The findings translate cleanly into clinic-selection criteria. A women's hormone clinic that is delivering care consistent with this evidence will:

• Run baseline labs before prescribing, including total testosterone, free testosterone, SHBG, estradiol, thyroid, iron studies, hemoglobin, and a metabolic panel.
• Treat broader symptom domains -- energy, mood, cognition -- when labs and history support androgen contribution, not just libido-only.
• Use individualized, biomarker-guided dosing rather than fixed-dose protocols.
• Re-check labs at 6 to 12 weeks during titration and at least annually thereafter.
• Use physiologic dosing (typically 4 to 6 mg per day transdermal for most women) and avoid supraphysiologic levels that produce side effects.
• Manage estradiol and progesterone in parallel for women who need them, rather than treating testosterone in isolation.

Clinics that prescribe high-dose pellets without titration, or fixed-dose creams without follow-up labs, or refuse to consider testosterone for non-libido symptoms despite supportive labs and history, are operating outside the evidence base this study reinforces. The women's HRT clinic comparison and the broader clinic comparison identify clinics that follow the evidence-based standards.

What Comes Next

The natural next step in the research is a randomized placebo-controlled trial of individualized testosterone therapy in women with broader symptom endpoints than HSDD alone. The signals from this study, the prior 510-woman pilot, the Australian dose-finding work, and the FDA's developing pathway for female-specific testosterone products are converging in the same direction: women's testosterone deserves a randomized evidence base that matches the breadth of how it is being prescribed.

For clinicians, the immediate practical effect is that the published evidence now better supports what experienced practitioners have been doing in clinic. For women considering treatment, the practical effect is that the conversation can now reference real peer-reviewed data on energy, mood, cognition, and biomarker changes -- not just libido outcomes from older trials.

For the broader field, the study reinforces the importance of telehealth-based hormone platforms that can both deliver individualized care at scale and contribute structured outcomes data back into the literature. That feedback loop is how the evidence base will fill in over the coming years.

Related Reading

• Best Online HRT Clinic for Women -- evidence-based women's hormone clinic comparison
• Testosterone for Women: Complete Guide -- foundational overview
• Testosterone Women Dosage Guide -- dosing for cream, gel, pellets
• Testosterone and Anxiety in Women -- mood biology and prior 510-woman study
• HRT and Brain Fog -- cognitive symptoms framework
• Acrux Female Testosterone Phase 3 -- the FDA pathway for women's testosterone
• HRT Black Box Warning Removed -- the broader evidence-based re-evaluation of women's hormone therapy

References

1. Bikman B, Reynolds P. Testosterone Replacement Therapy in Women Is Associated with Improved Symptom Burden and Favorable Biomarker Changes: A Retrospective Observational Study. Journal of Personalized Medicine. 2026;16(5):231. MDPI Publication
2. Business Wire. New Study Shows Testosterone Therapy in Women Significantly Improves Energy, Mood, and Quality of Life. May 7, 2026. Business Wire
3. Morningstar / Las Vegas Sun. New Study Shows Testosterone Therapy in Women Significantly Improves Energy, Mood, and Quality of Life. May 7, 2026. Las Vegas Sun
4. Davis SR, Baber R, Panay N, et al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019;104(10):4660-4666. PMC Article
5. Glaser RL, et al. Effect of transdermal testosterone therapy on mood and cognitive symptoms in peri- and postmenopausal women. 2024 pilot study. PMC Article

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