Anastrozole (Arimidex) generally appears to have the most neutral, “least bad” overall effect on lipids compared with exemestane (Aromasin) and letrozole (Femara) in the main head‑to‑head data, even though all three third‑gen AIs are considered clinically acceptable from a lipid standpoint.​

What the LEAP study showed

The LEAP (Letrozole, Exemestane, Anastrozole Pharmacological) trial compared these three AIs in healthy postmenopausal women over 24 weeks and specifically looked at safety markers including lipid profiles. Key points:​

• Anastrozole: No significant adverse changes in standard lipid parameters were found; it did not significantly worsen LDL:HDL ratios or triglycerides in this setting.​
• Letrozole: Was associated with a significant increase in triglycerides, but without major shifts in atherogenic ratios compared with anastrozole.​
• Exemestane: Showed a small reduction in total cholesterol in some analyses, but produced a significant increase in the LDL:HDL cholesterol ratio and in the ApoB:ApoA1 ratio compared with the other two, which are both considered more atherogenic patterns.​

Clinically, oncologists often describe these differences as “modest” and not a reason to avoid any particular AI outright, but they are still meaningful for anyone who already has borderline or poor lipids.​

Why the usual “Aromasin is best” line is too simple

On forums, the mantra is often:

• “Letro is the worst for lipids.”
• “Aromasin (exemestane) is the safest for lipids.”

The more detailed data complicates that:

• Several studies and reviews note that all third‑gen AIs tend to slightly worsen lipid profiles compared with tamoxifen, but differences between anastrozole, letrozole and exemestane are relatively small and sometimes inconsistent across trials.​
• The LEAP and related analyses specifically flag exemestane as the one that increases LDL:HDL and ApoB:ApoA1 ratios compared with anastrozole and letrozole, even when total cholesterol and triglycerides might look a bit better on paper.​

From a cardiovascular‑risk point of view, a higher LDL:HDL and higher ApoB:ApoA1 are not what you want, especially if your HDL is low to begin with.

Where Anastrozole fits in

Pulling it together:

• Anastrozole tends to show minimal or no significant change in most lipid measures, with some meta‑analyses suggesting small decreases in total cholesterol and HDL but no clear worsening of LDL or triglycerides overall.​
• Letrozole can raise triglycerides and sometimes LDL, depending on duration and population, though results are mixed across studies.​
• Exemestane may slightly lower total cholesterol and triglycerides in some long‑term series, but at the cost of shifting LDL:HDL and ApoB:ApoA1 in a more atherogenic direction compared with anastrozole.​

So if the specific question is “Which AI seems to disturb lipids the least overall?”, the evidence backs your take: anastrozole comes out as the most rounded and benign on lipids, exemestane is not the magic “lipid‑friendly” AI it’s often claimed to be, and letrozole is the roughest on triglycerides.