Written by Keen Meds · Reviewed by Licensed Clinical Providers · March 1, 2026
Key Insight: Saad et al. (Aging Male 2022) followed men on continuous testosterone therapy for up to 12 years and found sustained, progressive improvements in body weight, waist circumference, HbA1c, blood pressure, and lipid profiles maintained throughout the entire follow-up period.
Randomized controlled trials are the gold standard for evaluating whether a treatment works. But most RCTs have a practical limitation: they last one to three years. For a treatment like testosterone replacement therapy, which is typically maintained long-term, a two-year trial cannot tell you what happens at year five, year eight, or year twelve. Does the benefit plateau and then reverse? Does a new safety signal emerge over time? Do the metabolic improvements compound or fade? These questions require real-world data collected over many years, and they are exactly what Saad and colleagues set out to answer. Published in The Aging Male in 2022, their 12-year registry study represents the longest continuous follow-up dataset on TRT outcomes published in the scientific literature.
The Study: A 12-Year Real-World Registry
Farid Saad and colleagues followed men with testosterone deficiency who received continuous long-acting injectable testosterone undecanoate (the formulation marketed as Nebido in Europe and Aveed in the United States) at a single clinical center in Germany. This formulation is administered by injection every 10 to 14 weeks, providing stable testosterone levels with relatively infrequent dosing.
The registry enrolled men at the point of TRT initiation and followed them for up to 12 years, collecting data at regular intervals on a comprehensive set of clinical and metabolic outcomes. This design makes it an observational registry study rather than a randomized controlled trial. All participants received treatment -- there was no placebo group. This is the primary methodological limitation and must be held in mind when interpreting results.
The outcomes tracked included body weight, body mass index (BMI), waist circumference, HbA1c (a marker of blood glucose control), blood pressure, lipid profiles (total cholesterol, HDL, LDL, triglycerides), sexual function, and quality of life measures. The breadth of these outcomes across such a long follow-up period is what makes this dataset uniquely valuable.
What 12 Years of Data Showed: Sustained, Progressive Benefits
The findings of the Saad 2022 registry study did not suggest a treatment benefit that appeared early and then plateaued or reversed. Instead, the data showed that improvements were progressive -- they continued to accumulate over the 12-year follow-up period.
On body weight and waist circumference, men showed consistent, progressive reductions over time. Body weight declined over the first several years and remained reduced throughout follow-up. Waist circumference -- a proxy for visceral adiposity and metabolic risk -- similarly declined and stayed reduced. This is notable because many metabolic interventions produce initial benefit followed by gradual reversal as adherence wanes or tolerance develops. In this cohort, the body composition benefit was sustained.
On glycemic control, HbA1c improved progressively over time. This is particularly significant because HbA1c reflects long-term blood sugar control -- it averages glucose levels over approximately three months. Consistent, progressive HbA1c improvement over 12 years suggests a durable effect on insulin sensitivity and glucose metabolism, consistent with the T4DM trial findings in the shorter-term RCT setting.
Blood pressure improved across both systolic and diastolic measures. Lipid profiles showed reductions in total cholesterol and LDL, with some evidence of HDL improvement. These cardiovascular risk markers moved consistently in a favorable direction throughout the follow-up period.
Sexual function and quality of life measures, including validated questionnaires on erectile function, libido, and general wellbeing, showed sustained improvement. There was no signal of declining benefit in sexual or psychological outcomes over time.
Why Long-Duration Data Matters for TRT Decisions
One of the most common concerns patients and providers raise about testosterone therapy is the question of what happens over many years. Will benefits last? Will new risks emerge? The existence of RCT data covering one to two years is reassuring for short-term decisions, but TRT is typically a lifelong commitment once started, which means longer-duration evidence is essential for fully informed decision-making.
The Saad registry study addresses this gap with 12 years of real-world data. It establishes that the metabolic and body composition benefits observed in shorter RCTs do not appear to be transient -- they persist and, in this cohort, continued to improve over time.
From the perspective of biological plausibility, this makes sense. Testosterone deficiency is a chronic condition. Its metabolic consequences -- visceral fat accumulation, insulin resistance, dyslipidemia, reduced muscle mass -- develop gradually over years. Reversing those consequences through testosterone normalization should also occur gradually, and the benefits may compound as body composition improves further and the body responds to a sustained hormonal environment.
Limitations to Interpret Carefully
The Saad registry has important methodological limitations that are essential to understand. As an observational registry without a control group, it cannot exclude the possibility that other factors -- the clinical attention received, lifestyle changes prompted by engaging with medical care, secular trends over 12 years -- contributed to the outcomes. This is the foundational limitation of any uncontrolled registry.
Survivorship bias is also a relevant concern. Men who remained in continuous treatment for 12 years are not a representative sample of all men who started TRT. Some men stop treatment due to side effects, dissatisfaction, illness, or other factors. The long-term cohort may be selectively composed of men who tolerated and benefited from therapy -- making the outcomes look more positive than they would be in an unselected starting population.
The formulation used -- injectable testosterone undecanoate every 10 to 14 weeks -- is different from daily transdermal spray or gel. Pharmacokinetic differences between formulations affect how testosterone levels behave over time and may influence metabolic outcomes to some degree.
Despite these limitations, the Saad data is currently the best available real-world evidence on long-term TRT outcomes and provides meaningful reassurance that the benefits seen in shorter trials are not temporary.
Frequently Asked Questions
How is the Saad registry different from a clinical trial like TRAVERSE?
The Saad registry is an observational study without a control group -- it tracked outcomes in men who all received treatment, without randomization to a placebo group. This makes it better for understanding what happens over very long periods, but it cannot establish causation the way a randomized trial can. The TRAVERSE trial was a randomized controlled trial with an average follow-up of 33 months. The Saad registry extends follow-up to 12 years but with less internal validity. They address different but complementary questions.
Do the benefits of testosterone therapy compound over time, or do they plateau?
The Saad data suggests they continue to progress rather than plateau, at least through 12 years. Body composition improvements, HbA1c reductions, and lipid improvements all continued throughout the follow-up period in this cohort. This is consistent with the idea that reversing the metabolic consequences of long-standing testosterone deficiency takes time and that the underlying physiology responds progressively to sustained hormone normalization.
Does the 12-year dataset show any safety signals that shorter studies miss?
The Saad registry did not identify new major safety signals emerging specifically at longer follow-up durations. Polycythemia and PSA changes were monitored and managed as part of standard clinical care throughout the 12-year period. No unexpected late-emerging adverse effects were reported. This is reassuring, though the observational nature of the study means definitive safety conclusions require corroboration from other sources.
Is the formulation used in the Saad study the same as testosterone spray?
No. The Saad study used long-acting injectable testosterone undecanoate (Nebido/Aveed), administered every 10 to 14 weeks. Testosterone spray is a daily transdermal formulation with a different pharmacokinetic profile. The metabolic biology addressed in the Saad study is broadly applicable, but the specific dose-response relationships and hematocrit effects differ between formulations. Daily transdermal delivery typically produces lower and more stable testosterone levels, with a lower rate of polycythemia.
What This Means for Your Treatment Decisions
The Saad 12-year registry study addresses the most important question that shorter trials cannot: what happens over a decade of continuous testosterone therapy? The answer from this dataset is that the metabolic, body composition, and quality of life benefits appear to be durable and progressive -- not temporary or fading. For men considering whether TRT is a long-term commitment worth making, this is among the most relevant evidence available.
Keen Meds connects you with licensed clinical providers for a telehealth evaluation and lab review. If your testosterone is clinically low, you may qualify for Testosterone Spray Rx.
