Anastrozole

What it is

Anastrozole blocks aromatase, the enzyme that converts testosterone into oestradiol. In postmenopausal breast cancer, where tumour growth can be oestrogen-driven, that is the therapeutic point and it is well established.

In men it does something predictable: testosterone rises, oestradiol falls. A one year randomised, double-blind, placebo-controlled trial in 88 men aged 60 and over with low testosterone found levels rising from about 11.2 to 18.2 nmol/L by month three on 1 mg daily.

Why the trial result is not the whole story

Raising testosterone is easy to measure and easy to be pleased by. Whether men feel or function better is a separate question, and the trials have been much less impressive on that front than on the hormone panel.

The reason is that oestradiol is not a contaminant in male physiology. It maintains bone density, supports libido, and contributes to lipid handling. Suppressing it to look better on a lab report is a category error, and it is the single most common one in this corner of the internet.

The bone data makes the point. A twelve week randomised study in elderly mildly hypogonadal men found anastrozole lowered oestradiol without harming bone metabolism over that window, which sounds reassuring until you notice the window. Twelve weeks is not how long people take this.

The off-label pattern, honestly

Anastrozole gets used alongside testosterone replacement to control aromatisation, frequently pre-emptively, before any symptom or measurement suggests a problem.

Two things go wrong with that. The first is that most men on reasonable testosterone doses never need it. The second is that the doses used are guesses. Trials used 1 mg daily. Common practice is a quarter tablet twice a week, a regimen with no dose-finding study, chosen because full doses crushed oestradiol so hard that people felt terrible.

When someone on testosterone reports low libido, flat mood and aching joints, over-suppressed oestradiol is at least as likely an explanation as the reverse, and it is far less often considered.

Practical notes

• Treat symptoms, not numbers. There is no established optimal oestradiol level for men on testosterone therapy, and chasing an arbitrary target is how people medicate themselves into feeling worse.
• Use the right assay. Standard immunoassays perform poorly at male oestradiol concentrations. The sensitive assay, run by liquid chromatography mass spectrometry, is the one that gives a meaningful number.
• Lowering the testosterone dose is usually the better lever. Aromatisation scales with substrate. Adding a second drug to counteract the first is the more complicated fix and the more fragile one.
• Long-term skeletal risk is the real open question. Every study reassuring about bone is short. Men take this for years.

Side effects and warning signs

Commonly reported

• Joint aches and stiffness, the most characteristic complaint of the class
• Reduced libido, which is what happens when oestradiol goes too low in men
• Fatigue
• Hot flushes
• Adverse shifts in lipid profile

Stop and get medical help

• Bone pain or a fracture from minor trauma. Oestradiol maintains bone density in men as well as women, and suppressing it has skeletal consequences
• Persistent low mood or loss of libido that worsens as the dose increases, which usually means oestradiol is too low rather than too high

Sources

1. Burnett-Bowie et al., Effects of aromatase inhibition in hypogonadal older men, randomised placebo-controlled trialtrial
2. Effect of aromatase inhibition on bone metabolism in elderly hypogonadal mentrial

From the community

Discussion for this compound concentrates in r/Testosterone and r/trt.

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