Testosterone Therapy Shows No Benefit for Women With Early Heart Failure

At the Australian Menopause Society Annual Congress in Sydney, Dr. Julia Grant presented results from a clinical trial that tested a straightforward hypothesis: could testosterone therapy help women with early heart failure? The answer, it turned out, was no—but the way researchers arrived at that answer matters as much as the conclusion itself.

Heart failure with preserved ejection fraction, or HFpEF, is a condition where the heart muscle loses its ability to relax properly between beats, leaving it unable to fill with blood as it should. The blood vessels themselves may also stiffen. Beyond the cardiovascular system, the condition damages skeletal muscle, which atrophies and becomes infiltrated with fat. Women make up 55 to 65 percent of people living with HFpEF, though new diagnoses occur at similar rates in both sexes—the gender imbalance likely reflects that women tend to live longer with the disease. For women specifically, high blood pressure, type 2 diabetes, and obesity carry outsized risk. Pregnancy complications like preeclampsia and gestational diabetes also increase vulnerability, as do the hormonal shifts of menopause. The hallmark symptom is exercise intolerance, often accompanied by fatigue, breathlessness, and fluid retention.

The biological case for testosterone was plausible. Testosterone improves how blood vessels dilate, builds skeletal muscle, and enhances oxygen utilization. Women's testosterone levels decline with age, and HFpEF incidence climbs in parallel. Testing whether supplementation could restore exercise capacity in postmenopausal women over 55 seemed worth pursuing. The Australian Heart Foundation funded the work, and the investigators designed a rigorous study: a randomized, placebo-controlled crossover trial in which women took either testosterone or placebo for four months, then underwent a four-week washout, then switched to the other treatment. Neither participants nor researchers knew which women were receiving which medication at any given time. The primary measure was peak oxygen uptake relative to body weight during maximal exercise. Secondary measures included cardiac function assessed by echocardiogram, quality of life, and cardiac MRI scans in a subset of participants. The team calculated they needed 38 women to complete the study to detect a clinically meaningful change.

The testosterone dose was calibrated to achieve typical premenopausal levels. When women took the hormone, their testosterone rose from an average of 0.76 nmol/L to 1.15 nmol/L—the intervention worked as intended. But the primary outcome did not budge. There was no clinically meaningful improvement in peak oxygen uptake. Secondary measures showed the same pattern: no improvement in quality of life, no improvement in cardiac or muscle function compared with placebo. An exploratory analysis found a small increase in left ventricular mass in the testosterone group, but Dr. Grant herself questioned whether this was a genuine effect or statistical noise. The final peer-reviewed paper, not yet published at the time of the presentation, may shed more light on that finding.

One limitation worth noting: the average age of enrolled women was about 72, somewhat older than the target range of late 50s to early 60s. Screening over 170 women to enroll the final cohort suggests recruitment was challenging. Dr. Grant acknowledged this candidly. Finding women in their late 50s and early 60s who met the specific criteria for early HFpEF may simply have been difficult. Younger women might have been unable to commit to multiple in-person visits due to work and family obligations. Clinical trials demand a lot from participants—repeated visits, medication adherence, willingness to take an unproven treatment or placebo. The logistics alone exclude many people.

What this trial represents is evidence-based medicine functioning as it should. A biologically sound hypothesis was tested in a well-designed study with appropriate rigor. The intervention achieved its intended effect on hormone levels but failed to improve the outcomes that matter to patients. This is not a failure of the research; it is the research doing its job. The results are neither good nor bad—they are simply what they are: another piece of the puzzle, another boundary drawn around what works and what does not. Women deserve this kind of careful, honest investigation. The final publication will likely provide additional context and interpretation, but the core finding stands: testosterone therapy, at least at premenopausal levels and over a four-month period, does not improve exercise capacity or quality of life in postmenopausal women with early heart failure.