Short answer: Some testosterone is turned into estradiol (E2) by the aromatase enzyme, so E2 rises on TRT. That is expected, and estradiol does real work in men: in one trial, blocking it raised body fat. Anastrozole and exemestane are FDA approved only for breast cancer in women. In a 1-year trial in older men, anastrozole lowered spine bone density. No guideline sets an E2 target for men on TRT.
| Compound | Best evidence | What it shows |
|---|---|---|
| Anastrozole (Arimidex) | Approved for a different use | Approved for breast cancer in postmenopausal women. In women it cut estradiol about 80% after 14 days. In older men, a 1-year trial found lower spine bone density than placebo. |
| Exemestane (Aromasin) | Approved for a different use | Approved for breast cancer in postmenopausal women. We found no randomized trial of exemestane in men on TRT. |
| Testosterone cypionate or enanthate | Approved for a different use | The source of the extra estradiol. In the Testosterone Trials, bigger rises in estradiol went with bigger gains in sexual desire and activity. |
"Animal or lab studies only" means no published human trial for this goal that we could find. Results in rats or cells often do not carry over to people. Compounds that are not FDA-approved have no tested label for dose, purity or safety.
Aromatase is an enzyme that converts androgens, such as testosterone, into estrogens, such as estradiol. The Arimidex label describes this pathway: estrogens mainly come from aromatase acting on androgens. More testosterone in the blood gives aromatase more to work with, so estradiol usually rises along with it.
The AUA guideline says it is "not uncommon" for estradiol to rise as testosterone rises on therapy, and that symptomatic gynecomastia or other breast symptoms are uncommon. It recommends measuring estradiol before treatment in men who already have breast symptoms or gynecomastia, and, for breast symptoms that start on treatment, a period of watching, since they sometimes settle.
The clearest experiment is Finkelstein 2013. Researchers shut down hormone production in 400 healthy men aged 20 to 50, then gave set doses of testosterone gel, with or without anastrozole to block estradiol, for 16 weeks. Low testosterone explained the loss of lean mass, muscle size and strength. Low estrogen mainly explained the rise in body fat. Both contributed to lower sexual function.
The Testosterone Trials point the same way for sex drive. In 470 men aged 65 or older with low libido, larger increases in total testosterone, free testosterone and estradiol were each linked to bigger improvements in sexual desire and activity, though not erectile function.
Bone is the other concern. In a 1-year randomized trial of 69 men aged 60 or older with low or borderline testosterone, anastrozole raised testosterone (from 319 to 474 ng/dL by 1 year) and lowered estradiol (15 to 12 pg/mL). Spine bone density fell on anastrozole and rose slightly on placebo. The authors concluded aromatase inhibition does not improve skeletal health in these men. The Arimidex label also reports lower spine and hip bone density in women.
No. Both labels approve these drugs only for breast cancer in postmenopausal women. The Arimidex label also describes a placebo-controlled trial in 80 boys with pubertal gynecomastia that did not show a benefit. Use on TRT is off-label, a decision for you and your prescriber.
| Drug | Approved use | Label note relevant to men |
|---|---|---|
| Anastrozole (Arimidex), 1 mg tablet | Breast cancer in postmenopausal women | Lowered bone density in women; no benefit for gynecomastia in pubertal boys |
| Exemestane (Aromasin), 25 mg tablet | Breast cancer in postmenopausal women | No approved use in men |
Studies in older men used anastrozole instead of testosterone, to raise the body's own testosterone. In a 12-week trial in 37 men aged 62 to 74, it raised total testosterone and lowered estradiol, with estradiol staying in the normal male range; the authors said the effects on health were still to be determined. The AUA guideline lists aromatase inhibitors only as one option for men who want to keep fertility. More context is in Estradiol (E2) on TRT.
Diagnosis and prescribing decisions belong with a licensed clinician who can examine you and order labs.
Terms on this page: Aromatase inhibitor (AI) · Trough level · Steady state