Testosterone

Most of these trials enrolled men by age rather than by a low testosterone reading, so many participants were not deficient. A gain in lean mass is not by itself a gain in anything a man would notice. In the 16-trial pooling, whose men averaged 77 years old, no musculoskeletal difference from placebo was left by 12 months, which could mean the effect fades or only that fewer trials reported that far out.

The relative risk of 8.14 runs across an interval from 1.87 to 35.40, which reflects how few men had the event rather than a precise estimate. It rests on four trials, and those trials needed to run only twelve weeks, short against how long testosterone is actually taken.

About 65 men were screened for every one enrolled, so these are not the men who walk into a clinic. One year of treatment is short against how long testosterone is actually taken. In the pooled analysis the sexual-desire interval ran from 0.01 to 0.34, close enough to zero to be worth naming.

The trial was powered for artery thickening rather than for sexual outcomes, so the null on sex is a secondary result rather than a definitive one. Its authors say plainly that it should not be read as establishing cardiovascular safety. Haematocrit and prostate-specific antigen both rose more on testosterone.

Men had to have a partner willing to attempt intercourse at least twice a month, which selects a particular and comparatively motivated group. Twelve outcomes were tested, so some of the ten significant ones may be the arithmetic of testing many things. And the missing threshold cuts both ways: it undercuts any single diagnostic cutoff, and it also means no reading identifies in advance who will benefit.

This is a snapshot, so it can say which symptoms travel with low testosterone and not whether raising it would relieve them. That fatigue and low mood failed to cluster is a statement about how symptoms group, not proof they have nothing to do with testosterone. Testosterone here was measured by mass spectrometry on morning samples, a stricter standard than much routine clinical testing, so the thresholds may not transfer to an ordinary lab result.

A guideline is expert synthesis rather than primary evidence, and by its own grading many of its recommendations rest on low-quality evidence. It was published in 2018, before the large cardiovascular safety trial reported. It is a United States society position, and other specialist societies set different cutoffs.

The mechanism account is an expert review rather than a systematic synthesis, and it describes recovery as highly variable rather than putting numbers on it. Its suggestion that newer short-acting oral and nasal formulations partly spare sperm production is preliminary and rests on no fertility outcomes. The guideline is expert synthesis, and by its own grading many of its recommendations sit on low-quality evidence.

Noninferiority means testosterone was not worse than placebo by more than a preset margin, which is a different statement from safe. The three excess events were not adjusted for multiple comparisons and the trial was not powered to find them. Doses were titrated into the low-to-mid normal range, so nothing here speaks to higher amounts. The trial was funded by testosterone manufacturers.

Whether testosterone harms the arteries is unresolved. The largest trial found no rise in major cardiac events; an imaging trial found more non-calcified plaque after a year. Nobody has shown whether that plaque turns into events.

The two-year trial was nested inside a cardiovascular safety study, so every man in it had heart disease or a high risk of it. In the meta-analysis the gain shrank in men with diabetes or obesity, who are a large share of those seeking treatment. And 2.31 points sits close to the smallest difference a man with mild erectile dysfunction would notice.

Whether testosterone helps erections is unsettled. Pooled trials found a gain, largest in men starting lowest; two later long trials found none, in less deficient men on different questionnaires, so the split may be about who was studied.

These were healthy men with normal testosterone taking defined, mostly short courses in contraception trials, not men on open-ended replacement or on the much larger doses used for physique. Recovery was faster with shorter treatment and shorter-acting preparations, both of which cut against long-term replacement. The endpoint is a sperm concentration of 20 million per millilitre, a fertility proxy rather than a pregnancy. The data stop in 2005.

Only one of the seven handgrip trials found a gain on its own; the pooled significance comes from combining mostly null results, over an interval running from 0.17 to 3.0 kgf. The leg-press result sits exactly at p = 0.05. Physical performance, the outcome closest to something a man would notice, did not improve, and rested on only two comparable trials.

Whether testosterone makes men stronger is unsettled. The pooled gains rest on mostly null trials and other studies found none, but a knee, a hand squeeze and a leg press measure different things and can disagree without any being wrong.

Each man was his own comparison, which handles his fixed characteristics but not a new illness or hospital stay that could prompt both a prescription and a clot. Only 7.8% of the men had a hypogonadism diagnosis code at all. A prescription record shows the drug was dispensed, not that it was taken.

Whether testosterone raises clot risk is unsettled. Insurance claims show about double the odds and the randomised trial no overall excess, yet both point the same way on clots in the lung, the part of the signal that has not gone away.

Normal here means the middle third of the men surveyed, a statistical convention rather than a line anchored to symptoms or outcomes. Each man gave one measurement, where guidelines require two confirmatory morning readings. And knowing the range shifts with age does not show that treating young men against the higher number would help them; it would mainly widen who counts as deficient.

This compares whole markets rather than individual men, so it cannot show that any particular man was moved by an advert. Per exposure the effect is tiny, on the order of 0.05 extra initiations per 10,000 men per monthly exposure, even though the ratios are statistically significant. Advertising clustered in the southeastern states, which may differ in ways nobody measured. The data run to 2013, before direct-to-consumer telemedicine.

This reads what clinics say on their own websites, not what care they deliver or what happens to patients. The clinics were found by internet search, so the sample is neither exhaustive nor random. Website content changes, which dates the snapshot. And it describes the market around testosterone rather than saying anything about the drug itself.