Anastrozole is a medication that lowers estrogen levels in the body, primarily used to treat hormone receptor-positive breast cancer in postmenopausal women. Sold under the brand name Arimidex, it works by blocking an enzyme called aromatase, which is responsible for converting other hormones into estrogen. By cutting off this estrogen supply, anastrozole slows or stops the growth of breast cancers that depend on estrogen to spread.
How Anastrozole Works
After menopause, the ovaries stop producing estrogen, but the body still makes small amounts through a different pathway. An enzyme called aromatase, found in fat tissue and other organs, converts hormone precursors into estrogen. Anastrozole blocks this enzyme, reducing circulating estrogen levels by roughly 80%. Since many breast cancers have receptors that use estrogen as fuel for growth, dramatically lowering estrogen levels starves these tumors of the signal they need to multiply.
This mechanism is why anastrozole only works for hormone receptor-positive cancers. Tumors that don’t rely on estrogen for growth won’t respond to the drug.
Approved Uses in Breast Cancer
Anastrozole has three FDA-approved uses, all in postmenopausal women. The first and most common is as adjuvant therapy, meaning it’s taken after surgery to reduce the chance that early-stage hormone receptor-positive breast cancer comes back. The second is as a first-line treatment for locally advanced or metastatic breast cancer that is hormone receptor-positive. The third is for advanced breast cancer that has continued to grow despite prior treatment with tamoxifen, an older hormone-blocking drug.
The standard dose across all three uses is one 1 mg tablet taken once daily.
How It Compares to Tamoxifen
Tamoxifen was the go-to hormone therapy for breast cancer for decades, and anastrozole is now a common alternative. A large meta-analysis of over 7,000 women found that those taking an aromatase inhibitor like anastrozole had a lower rate of breast cancer recurrence compared to those on tamoxifen. The five-year recurrence rate was 6.9% with an aromatase inhibitor versus 10.1% with tamoxifen, a meaningful 3.2 percentage point difference. Distant recurrence, where cancer spreads to other parts of the body, was also reduced.
That said, the two treatments showed no significant difference in overall survival or breast cancer mortality. The recurrence benefit was concentrated in the first four years of treatment, with no additional advantage seen from years five through nine. Both drugs work, but anastrozole offers a measurable edge in keeping cancer from returning during the early years after treatment.
How Long Treatment Lasts
The standard course is five years. However, research has explored whether extending treatment to ten years offers additional protection. A randomized trial found that continuing anastrozole for a total of ten years improved disease-free survival compared to stopping at five: 91% of women in the extended group remained disease-free at five years of follow-up, compared to 86% in the group that stopped. No difference in overall survival was observed, though, so the decision to continue beyond five years is typically weighed on an individual basis, balancing the potential benefit against years of additional side effects.
Side Effects and Bone Health
Because anastrozole works by suppressing estrogen, and estrogen plays a key role in maintaining bone density, bone loss is the most clinically significant side effect. Data from a major clinical trial showed that women on anastrozole lost 6.1% of bone mineral density at the spine and 7.2% at the hip over five years. That’s a substantial decline and increases the risk of fractures over time.
To counteract this, women taking anastrozole are typically advised to take daily calcium and vitamin D supplements (commonly 500 mg of calcium and 400 IU of vitamin D) and to have bone density scans every one to two years while on the drug. Weight-bearing exercise and a healthy lifestyle also help protect bone strength during treatment.
Other common side effects include joint pain and stiffness, hot flashes, fatigue, and mood changes. Joint symptoms are one of the more frequent reasons women consider stopping treatment early, so they’re worth discussing with a prescriber if they become disruptive.
Who Should Not Take Anastrozole
Anastrozole is not effective in premenopausal women. Because the ovaries are still actively producing large amounts of estrogen before menopause, blocking the aromatase enzyme alone isn’t enough to lower estrogen to meaningful levels. Premenopausal women who need aromatase inhibitor therapy must first have their ovarian function suppressed through medication or surgery. Anastrozole is also not used in cancers that are hormone receptor-negative, since those tumors don’t depend on estrogen and rarely respond to the drug.
Off-Label Uses
Gynecomastia in Boys and Men
Anastrozole is sometimes prescribed off-label for males with gynecomastia, a condition where breast tissue enlarges due to a hormonal imbalance between estrogen and testosterone. In a randomized trial of boys aged 11 to 18 with pubertal gynecomastia, those taking anastrozole saw their testosterone-to-estrogen ratio increase by 166% over six months, compared to 39% in the placebo group. By lowering estrogen and allowing testosterone to dominate, the drug can help reduce breast tissue growth. It’s also used alongside testosterone replacement therapy in adult men to prevent estrogen-related side effects.
Ovulation Induction for Infertility
Anastrozole has been studied as an alternative to clomiphene citrate, the most widely used fertility drug for women who aren’t ovulating regularly. The theory is appealing: clomiphene has a long half-life and can deplete estrogen receptors over time, potentially thinning the uterine lining and reducing the chance of implantation. Anastrozole, by contrast, lowers estrogen levels without affecting the receptors themselves.
In practice, results have been mixed. A phase II trial of 271 women with ovulatory dysfunction found that clomiphene produced ovulation in about 65% of women in the first cycle, while anastrozole at various doses achieved only 30 to 37%. Over multiple cycles the cumulative ovulation rates narrowed, but anastrozole did not demonstrate equivalence to clomiphene. On the positive side, no cases of ovarian hyperstimulation syndrome were reported with either drug, and both were well tolerated. Anastrozole remains a second-line option for fertility, typically considered when clomiphene isn’t suitable or hasn’t worked.