A systematic review published in Frontiers in Endocrinology on February 11, 2026 set out to answer a question women considering testosterone therapy still hear from skeptical clinicians: does this hurt my heart? The short answer the data supports: no signal of harm at the doses women actually take. The long answer is more nuanced — and matters if you are weighing this decision now.
Key Takeaways
- 13 randomized controlled trials of 2,628 cisgender women on transdermal testosterone reported zero cardiovascular deaths
- All trials used low-dose physiological transdermal delivery (patches, gels, sprays)
- Follow-up was 8 to 52 weeks — adequate for short-term safety, not long-term
- Evidence certainty: moderate, downgraded for short follow-up
- Transgender men data (1.81 deaths per 1,000 person-years on full male-range dosing) is not comparable
- The review calls for adequately powered long-term trials in cisgender women
- Pellets and supraphysiological doses are NOT covered by this evidence base
What the 2026 Review Did
Researchers Diogo Pinto da Costa Viana, Lucas Caseri Câmara, and Lucio de Sousa Monte Alto pulled together two parallel evidence streams:
- Cisgender women using testosterone for low libido (HSDD) or related indications: 13 randomized controlled trials, 2,628 participants, follow-up 8 to 52 weeks
- Transgender men on gender-affirming testosterone therapy: 13 observational cohort studies, 7,837 participants, follow-up 1 year to several decades
These are different populations, different doses, and different study designs. The review treats them separately and explicitly warns against direct comparison.
The Cisgender Women Data
This is the data women considering testosterone for libido, mood, or postmenopausal symptoms care about most.
| Metric |
Result |
| Trials |
13 RCTs |
| Participants |
2,628 cisgender women |
| Cardiovascular deaths |
0 |
| Dose form |
Transdermal patches, gels, sprays |
| Dose target |
Upper end of female physiological range |
| Follow-up |
8 to 52 weeks |
| Certainty |
Moderate (downgraded for duration) |
Zero cardiovascular deaths in 2,628 women across 13 placebo-controlled trials is a meaningful absence. It does not prove long-term safety. It does mean that the short-term cardiac safety signal — which is what skeptics tend to invoke — is essentially flat.
The Transgender Men Data
The transgender men cohorts are a different question entirely. These men used full male-range testosterone for years, often decades. The review found 34 cardiovascular deaths across 7,837 patients, equaling 1.81 deaths per 1,000 person-years.
For context: the all-cause cardiovascular mortality rate in cisgender men of similar age ranges is generally in the same ballpark or somewhat higher. The transgender men data does not show a clear excess mortality signal vs comparable male populations, but the certainty was rated low to very low because:
- All studies were observational, not randomized
- Baseline cardiovascular risk factors were inconsistently adjusted
- Outcome definitions varied across studies
- Confounding by smoking, BMI, and metabolic status was incompletely addressed
The point of including this arm of the review is not to suggest that the cis-women data and trans-men data should average out. It is to acknowledge that long-term testosterone exposure has been studied — just in a different population, at a different dose, with weaker study designs.
Why "Zero Deaths" Is Both Reassuring and Insufficient
Two things can be true at once. Zero cardiovascular deaths in 2,628 trial participants is genuine reassurance. It is also not the same as proving long-term safety.
What "Zero" Tells Us
Cardiovascular events accumulate over time. In short-term trials (under one year), even high-risk populations show low absolute event rates. The fact that not a single woman in any of these 13 trials had a fatal cardiovascular event tells us:
- Acute cardiac toxicity is not a feature of low-dose transdermal testosterone in women
- The expected event rate at one year in this age group (mostly postmenopausal women, average age in the 50s and 60s) was low to begin with
- Any signal of harm strong enough to overwhelm the natural low event rate would have shown up
This is meaningful. Acute cardiac death from drug toxicity in trials usually shows up early. None of these trials showed it.
What "Zero" Cannot Tell Us
The trials are too short to detect:
- Atherosclerosis acceleration over 5 to 20 years
- Long-term effects on insulin resistance and metabolic syndrome
- Cumulative impact on lipid profiles
- Differential outcomes in women with pre-existing risk factors
The largest cardiovascular safety study in men — TRAVERSE — needed 5,246 participants and 33 months of follow-up to deliver definitive non-inferiority. The equivalent trial in women has not been run.
What This Means If You Are Considering Testosterone
The practical guidance, broken out by situation:
If You Are A Postmenopausal Woman With HSDD or Low-Libido Symptoms
The 2026 review is your strongest current evidence base. Transdermal testosterone, dosed to the upper end of the female physiological range, has zero short-term cardiovascular death signal across thousands of patient-years of trial data. The International Society for the Study of Women's Sexual Health (ISSWSH) supports this indication. Your conversation with a prescriber should focus on:
- Baseline lipid panel and blood pressure
- Cardiovascular history (any prior MI, stroke, DVT)
- Smoking status
- A 6 to 12 month follow-up plan to recheck labs
Our testosterone for women complete guide walks through the dosing landscape. Our best online HRT clinic for women review covers providers that do thorough cardiovascular intake and follow-up labs.
If You Have Established Cardiovascular Disease
The trials in the 2026 review largely excluded women with prior MI, stroke, or unstable cardiac disease. The reassurance does not directly transfer. You need:
- A cardiology consultation before starting
- Lower starting dose with closer monitoring
- Possibly transdermal-only (avoiding oral or pellet routes that produce supraphysiological peaks)
- A higher threshold for benefit-risk
This is not a contraindication. It is a more careful conversation. Some women with controlled CV disease and severe HSDD do start testosterone. Some do not. Shared decision-making is the standard.
If You Are Considering Pellets
Stop and reconsider. Pellets were not used in any of the trials in the 2026 review. The reassurance specifically applies to transdermal delivery — patches, gels, sprays, creams — at doses targeting upper-female physiological range.
Pellets in women routinely produce supraphysiological serum levels in the first 2 to 4 weeks after insertion and erratic levels at the cycle end. Major guideline bodies including ISSWSH and The Menopause Society have explicit cautions or non-endorsements for pellet therapy in women. Our testosterone pellets for women article covers the evidence and the risks.
If You Are Premenopausal
The 2026 review primarily included postmenopausal women. Premenopausal use of testosterone for HSDD, energy, or mood is off-label and on weaker evidence ground. The cardiovascular safety reassurance is even more provisional in this group. Most modern protocols start with addressing the underlying issue — perimenopause, contraceptive interaction, thyroid, sleep — before adding testosterone.
The Lipid Question
Cholesterol is the most-cited concern. Here is what the trial data showed:
- HDL cholesterol: Small reductions of 2 to 5 mg/dL in some studies, no change in others
- LDL cholesterol: No significant changes
- Total cholesterol: No significant changes
- Triglycerides: No significant changes
None of these reached clinical significance for cardiovascular risk reclassification in any of the trials. The HDL reduction is the one consistent signal across studies. Its long-term meaning at this magnitude is unclear — some clinicians weight HDL drops as cardiovascular risk amplifiers, others view small isolated HDL changes without changes in LDL as low-impact.
Oral testosterone, which is not used in modern female protocols, has historically shown larger HDL reductions. That is one of several reasons women's testosterone has settled on transdermal delivery.
How This Fits With the Broader 2025-2026 Hormone Therapy Reset
The 2026 cardiovascular safety review lands during a major shift in how hormone therapy is being prescribed and discussed:
The cumulative direction is clear: hormone therapy — both estrogen and testosterone, both for women and for men — has had its risk profile recalibrated downward by modern evidence. The 2026 women's cardiovascular review is one more brick in that wall.
Where the Evidence Gaps Remain
Three questions the 2026 review explicitly flags as unmet:
1. Long-Term Cardiovascular Outcomes in Cisgender Women
The longest trial included was 52 weeks. A trial of 3 to 5 years would resolve most of the residual uncertainty. None is currently funded at scale.
2. Higher-Risk Populations
Women with diabetes, prior MI, prior stroke, or strong family history were systematically excluded. Whether the safety signal holds in these subgroups is genuinely unknown.
3. Standardized Outcome Definitions
The review calls for "adequately powered, long-term studies with standardized cardiovascular outcome definitions." Different studies counted different events. A unified definition (e.g., the MACE composite used in TRAVERSE) would make future evidence directly comparable.
What to Watch Next
The next evidence inflection points are likely to be:
- AVA-291 phase 1 readouts (late 2026 / early 2027): A women-specific testosterone formulation will generate its own safety dataset
- Acrux phase 3 HSDD readout: A larger, longer trial of testosterone in women than has ever been run, with cardiovascular endpoints as secondaries
- Re-analyses of existing menopause hormone therapy trials with testosterone arms: Pulling cardiovascular data from KEEPS or ELITE secondary analyses
Plan on a 18 to 36 month horizon for definitive long-term women's cardiovascular data.
Bottom Line
The February 2026 Frontiers in Endocrinology systematic review did three things:
- Confirmed zero cardiovascular deaths across 2,628 cisgender women on transdermal testosterone in 13 randomized trials
- Acknowledged that the trials were short (under one year), so long-term safety remains an open question
- Called for adequately powered long-term trials with standardized outcome definitions
For most women considering testosterone for HSDD, postmenopausal libido, or related symptoms, this is the strongest reassurance the modern literature has produced. It does not replace individualized risk assessment, baseline labs, or follow-up monitoring. It does close the door on the "we just don't know if it's safe" objection that delayed prescribing for years.
If you are weighing testosterone now, the conversation has shifted: not "is this dangerous" but "is this right for my situation, my dose form, my baseline." Our best online HRT clinic for women review covers providers that handle that conversation properly — with intake bloodwork, transdermal default protocols, and follow-up cadence that catches the rare outlier early.
References
- Viana DPC, Câmara LC, Alto LSM. Cardiovascular mortality associated with testosterone therapy in cisgender women and transgender men: a systematic review. Frontiers in Endocrinology. Published February 11, 2026. PMID: 41757239.
- Davis SR, Baber R, Panay N, et al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. Climacteric. 2019;22(5):429-434.
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107-117. (TRAVERSE trial.)
- Zitzmann M, Aversa A, Corona G, et al. Cardiovascular safety of testosterone therapy — Insights from the TRAVERSE trial and beyond: A position statement of the European Expert Panel for Testosterone Research. Andrology. 2026.
- International Society for the Study of Women's Sexual Health (ISSWSH). Position statement on testosterone use in women. https://www.isswsh.org
- The Menopause Society. The 2022 Hormone Therapy Position Statement of The North American Menopause Society. Menopause. 2022;29(7):767-794.
- Islam RM, Bell RJ, Green S, et al. Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. Lancet Diabetes Endocrinol. 2019;7(10):754-766.
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