Testosterone
See our Evidence Standards for how we grade the research below.
What It Is
Testosterone is the primary androgen in men and a physiologically important hormone in women as well, produced by the testes, ovaries, and adrenal glands. It acts through the androgen receptor to support muscle protein synthesis, bone density, red blood cell production, libido, and mood, and a portion of circulating testosterone is converted by the enzyme aromatase into estradiol, meaning some of testosterone's effects are mediated through estrogen receptors rather than androgen receptors directly.
The Evidence
In Men
Lincoff AM, Bhasin S, Flevaris P, et al.; TRAVERSE Study Investigators. "Cardiovascular Safety of Testosterone-Replacement Therapy." New England Journal of Medicine. 2023 Jul 13;389(2):107-117. Phase 4, randomized, double-blind, placebo-controlled, noninferiority safety trial. 5,246 men aged 45-80 with hypogonadism (two fasting testosterone levels below 300 ng/dL) and either existing cardiovascular disease or elevated cardiovascular risk were randomized to daily transdermal 1.62% testosterone gel or matching placebo, followed for a mean of 33 months. On the primary endpoint, a composite of cardiac death, non-fatal heart attack, and non-fatal stroke, testosterone was noninferior to placebo (occurring in about 7% of both groups). Secondary analyses found a higher rate of pulmonary embolism, atrial fibrillation, and acute kidney injury in the testosterone group. Two contextual factors are worth weighing when interpreting those secondary signals: the population was specifically selected for existing cardiovascular disease or high cardiovascular risk, and the trial's roughly 33-month mean follow-up period ran substantially through 2020-2022, overlapping the COVID-19 pandemic, during which population-wide rates of thromboembolic events and arrhythmias were independently elevated. Neither factor has been formally isolated as the explanation in a published reanalysis we could locate, so this is reasonable interpretive context rather than a settled explanation, and it doesn't erase the signal, but it's a relevant caveat before treating the secondary findings as a clean testosterone-specific safety story. Roughly 61% of participants in both arms discontinued treatment before the study ended, a real limitation the trial's authors acknowledged, though discontinuation rates were similar between groups.
Finkelstein JS, Lee H, Burnett-Bowie SA, et al. "Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men." New England Journal of Medicine. 2013 Sep 12;369(11):1011-1022. Randomized, blinded trial in 400 healthy men aged 20-50. All participants received a GnRH agonist to suppress their own testosterone and estradiol production, then were randomized to placebo or one of four testosterone gel doses for 16 weeks; half of each dose group also received an aromatase inhibitor to block conversion of testosterone to estradiol, isolating testosterone's effects from estradiol's. Changes in lean mass, thigh-muscle area, and leg-press strength tracked with testosterone dose specifically, regardless of estradiol level. Body fat percentage and sexual desire, however, tracked with estradiol level; blocking estradiol conversion (even at a fixed testosterone dose) was associated with more body fat gain and greater decline in sexual desire than the same testosterone dose without aromatase blockade.
Snyder PJ, Bhasin S, Cunningham GR, et al.; Testosterone Trials Investigators. "Effects of Testosterone Treatment in Older Men." New England Journal of Medicine. 2016 Feb 18;374(7):611-624. PMID: 26886521. The Testosterone Trials were a coordinated program of seven double-blind, placebo-controlled trials in 790 men aged 65 and older with low testosterone (average of two measurements below 275 ng/dL) and symptoms suggestive of hypogonadism, treated with testosterone gel or placebo for one year, dose-adjusted to the mid-normal range for young men. This paper reports the three primary trials: sexual function improved meaningfully with testosterone (the trial's clearest positive result); mood and depressive symptoms improved modestly; the Vitality Trial's primary endpoint (energy) did not show a significant benefit; and walking distance in the Physical Function Trial improved only modestly and inconsistently across analyses. Four further coordinated trials in the same program examined bone density, cognition, anemia, and cardiovascular effects; bone density and strength improved modestly, anemia in men with unexplained low hemoglobin was corrected, and cognitive function did not improve.
Budoff MJ, Ellenberg SS, Lewis CE, et al.; Testosterone Trials Investigators. "Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone." JAMA. 2017 Feb 21;317(7):708-716. PMID: 28241355. The Cardiovascular sub-trial within the same Testosterone Trials program, in 170 of the 788 participants (88 testosterone, 82 placebo) across 9 academic centers, measured noncalcified coronary artery plaque volume by CT angiography before and after 12 months of treatment. Testosterone was associated with a significantly greater increase in noncalcified and total coronary plaque volume than placebo. The increase was concentrated in fibrous plaque, which the authors noted may be more biologically stable than other plaque types, and they were explicit that a trial of this size and duration could not determine whether the finding translates into actual cardiovascular events. This is a genuine caution worth weighing seriously, not a settled harm; it's also part of why the much larger TRAVERSE trial, which directly measured cardiovascular events rather than plaque volume, was needed and reassuring on the harder outcome.
In Women
Achilli C, Pundir J, Ramanathan P, Sabatini L, Hamoda H, Panay N. "Efficacy and Safety of Transdermal Testosterone in Postmenopausal Women With Hypoactive Sexual Desire Disorder: A Systematic Review and Meta-Analysis." Fertility and Sterility. 2017 Feb;107(2):475-482.e15. PMID: 27916205. Meta-analysis of 7 randomized, double-blind, placebo-controlled trials, 3,035 postmenopausal women (naturally or surgically menopausal, on or off concurrent estrogen therapy), randomized to transdermal testosterone patch or placebo. Testosterone significantly increased satisfying sexual episodes, sexual desire, sexual activity, and orgasm compared with placebo. There was no significant difference in total or serious adverse events between groups, but testosterone was associated with significantly more androgenic side effects specifically (acne, increased hair growth) than placebo. No serious adverse events were attributed to treatment.
Islam RM, Bell RJ, Green S, Page MJ, Davis SR. "Safety and Efficacy of Testosterone for Women: A Systematic Review and Meta-Analysis of Randomised Controlled Trial Data." Lancet Diabetes & Endocrinology. 2019 Oct;7(10):754-766. A systematic review and meta-analysis of 46 reports from 36 blinded, randomized, placebo-controlled trials (at least 12 weeks' duration, published 1990-2018), covering 8,480 women. The review examined effects on sexual function, cardiometabolic markers, cognitive measures, and musculoskeletal health. Testosterone was associated with improvement in sexual function measures, particularly for postmenopausal women with low sexual desire. The authors noted that evidence for non-sexual outcomes and long-term safety, particularly cardiovascular and metabolic risk, remained more limited, since most included trials were relatively short in duration and not designed or powered to detect rare long-term safety events.
Hernandez BS, Boyne AM, Fleming B, Saffati G, Benton JZ, Hinojosa-Gonzalez DE, Dunnam S, Gudlavalleti H, Kamal A, Neville A, Lichtveld G, Khera M, Newson L. "Improvement in Multiple Organ Systems Following Testosterone Replacement Therapy in Women Previously on Standard Hormone Replacement Therapy." The Journal of Sexual Medicine. 2026;23(9):qdag116. DOI: 10.1093/jsxmed/qdag116. Retrospective cohort of 279 women (mean age 56, mean BMI 24.8) already established on stable transdermal estrogen therapy for at least three months, who then had transdermal testosterone added and were followed for roughly four months. Fifteen of twenty-four symptoms on a modified Greene Climacteric Scale improved significantly, including vaginal dryness, hot flashes, and libido; six of eight symptom clusters improved. This is broader-than-HSDD real-world evidence, but it carries real limitations worth stating plainly: there was no control group, the symptom instrument was a modified, non-validated scale, some participants had other hormone doses adjusted at the same time, every participant started at the same testosterone dose regardless of resulting serum levels, and the cohort likely skewed toward more symptomatic women than the general population. It's a promising early signal, not settled proof, presented here as a current, peer-reviewed extension of the evidence base rather than a replacement for the HSDD-specific trials above.
What's Reported in Practice
Beyond what the trials above directly measured, patients commonly report improvements in energy, motivation, and overall sense of vitality on testosterone therapy, in both men and women. Worth noting honestly: the Vitality Trial within the Testosterone Trials program tested energy and vitality directly as a primary endpoint and did not find a statistically significant benefit over placebo, even though sexual function and mood did improve in the same participants. That's a real tension between what's commonly reported and what the one trial designed to test it specifically found, and we think it's more honest to name that directly than to let the anecdotal reports stand unchallenged. Mood, motivation, and general sense of wellbeing outside the specific "vitality" construct tested remain plausible areas where reported experience may be picking up something the trial's specific instrument didn't fully capture, but that's speculation on our part, not a demonstrated finding.
What the Research Doesn't Yet Show
This is where we're most eager to see more research investment, not a mark against the therapy. TRAVERSE is reassuring on its primary cardiovascular endpoint but tested only one formulation (transdermal gel) in a specific population (men with existing or high cardiovascular risk), so its findings don't automatically generalize to injectable testosterone or to lower-risk men. The secondary safety signals it found (pulmonary embolism, atrial fibrillation, kidney injury) deserve continued study rather than being set aside because the headline finding was reassuring, and a dedicated analysis separating out how much of that signal reflects the high-risk population versus the pandemic-era follow-up window versus testosterone itself would meaningfully sharpen the picture; that analysis doesn't yet exist as far as we've found. The coronary-plaque finding from the T-Trials Cardiovascular sub-study and TRAVERSE's reassuring hard-outcome data sit somewhat in tension with each other, an imaging biomarker moving the wrong direction alongside no increase in actual cardiac events, and reconciling exactly what that combination means is an open question rather than a contradiction we can resolve for you here. In women, the evidence base is considerably thinner than in men: the largest meta-analysis available is limited mostly to short-duration trials focused on sexual function, and long-term cardiovascular and metabolic safety data in women remains genuinely limited, which is a large part of why no product is FDA-approved for women in the US despite widespread off-label and compounded use. Well-powered, long-duration outcome trials in women, and trials of non-transdermal formulations in men, are the clearest opportunities for this evidence base to grow.
FDA-approved for men with diagnosed hypogonadism. Used off-label and via compounded formulations in other contexts, including in women, where no FDA-approved product currently exists in the US. Sourcing and formulation are discussed at your visit.
Next Step
This page covers mechanism and evidence. Dosing, formulation, monitoring, and whether this is appropriate for you are individual clinical decisions made with your provider.
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