AI / Oral / 0.25-1mg EOD to daily
Anastrozole
Anastrozole came out of a deliberate search for a drug that would switch off estrogen synthesis without disturbing the rest of the adrenal steroid pathway, which is the problem the first-generation inhibitor aminoglutethimide never solved. ICI Pharmaceuticals and its successor Zeneca took the compound, then called ZD1033, to FDA approval in December 1995 for breast cancer in postmenopausal women; the men who now take it for estrogen control alongside testosterone arrived later and entirely off-label.
In plain words
Anastrozole is a tablet that blocks aromatase, the enzyme the body uses to turn testosterone into estrogen, so it lowers estrogen levels. It was approved in the United States in December 1995 to treat breast cancer in postmenopausal women, and large randomized trials support it for that. Men who take testosterone use it off-label to hold their estrogen down, but the randomized trials in men enrolled older or low-testosterone men, some on replacement doses and some on nothing at all, so the population using it off-label is not the population that was tested. One of those trials asked directly whether lowering estrogen this way helps older men's bones and found the opposite: spine bone density got worse. Men who use it this way most often report over-suppression rather than too little effect, and because a change takes about a week to settle in the blood, the joint pain, low libido, flat mood and poor sleep they describe show up days later.
At a glance
| Half-life | 1.95 days |
|---|---|
| Tmax | 0.04 days |
| Route(s) | Oral |
| Published dosing range | 0.25-1mg EOD to daily |
Reference data from the DosePlot canon -- not a protocol recommendation.
Serum curve
Single 0.625 mg dose by Oral, rendered from the same engine that powers the interactive chart. Relative levels, not lab values.
What does the evidence show?
Two things are labeled separately here because they answer different questions. The tier is how a study was built. The distance chips are whether that study touched this molecule, by this route, in a population resembling the reader. A randomized trial of a different molecule keeps its tier and still says nothing about this compound.
| Finding | Tier | Distance from use | Study |
|---|---|---|---|
| In healthy postmenopausal volunteers, 0.5, 1 and 3 mg daily each cut serum estradiol by about 80 percent from baseline, with no overall difference between the 0.5 and 1 mg doses. Counting the volunteers whose estradiol fell below the assay's detection limit suggested 1 mg was the smallest dose giving maximal suppression. Gonadotropins did not change, adrenal steroids did not change, and the steroid response to an ACTH challenge was unimpaired. Estradiol had still not recovered 144 hours after the last dose. | clinical | not recorded | Yates RA, Dowsett M, Fisher GV, Selen A, Wyld PJ. Arimidex (ZD1033): a selective, potent inhibitor of aromatase in postmenopausal female volunteers.British Journal of Cancer 73(4):543-548, 1996 |
| Twelve postmenopausal women with breast cancer took 1 mg and 10 mg daily for 28 days each in a randomized double-blind crossover. Whole-body aromatization fell from 2.25 percent at baseline to 0.074 percent on 1 mg and 0.043 percent on 10 mg, a mean inhibition of 96.7 and 98.1 percent. Plasma estrone, estradiol and estrone sulfate fell by at least 86.5, 83.5 and 93.5 percent, with no difference between the doses. A tenfold dose increase bought 1.4 percentage points of extra enzyme inhibition. | rct | not recorded | Geisler J, King N, Dowsett M, Ottestad L, Lundgren S, Walton P, Kormeset PO, Lonning PE. Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer.British Journal of Cancer 74(8):1286-1291, 1996 |
| At ten years in the ATAC trial, five years of 1 mg daily beat tamoxifen on time to recurrence in hormone-receptor-positive disease (hazard ratio 0.79, 95 percent confidence interval 0.70 to 0.89) with little difference in overall survival (0.95, 0.84 to 1.06). Fractures were more common while patients were on anastrozole (451 against 351, odds ratio 1.33) and no more common after treatment ended (110 against 112, odds ratio 0.98). The skeletal cost tracked exposure and stopped when the drug stopped. | rct | not recorded | Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial.Lancet Oncology 11(12):1135-1141, 2010 |
| Thirty-seven men aged 62 to 74 with screening testosterone below 350 ng/dL were randomized, double-blind, to 1 mg daily (n = 12), 1 mg twice weekly (n = 11) or placebo (n = 14) for 12 weeks. In the daily arm bioavailable testosterone rose from 99 to 207 ng/dL and total testosterone from 343 to 572 ng/dL, while estradiol fell from 26 to 17 pg/mL, all against placebo at p below 0.001. Luteinizing hormone rose from 5.1 to 7.9 units per liter, which is the mechanism: in men the feedback loop is intact, so taking estradiol away lifts the pituitary's drive. The twice-weekly arm raised total testosterone less (397 to 520 ng/dL, p = 0.012 against the daily arm) and lowered estradiol just as much (27 to 17 pg/mL). Hematocrit and the quality-of-life, erectile-function and prostate-symptom scores did not change. Prostate-specific antigen rose in the twice-weekly arm only, from 1.7 to 2.2 ng/mL (p = 0.031 against placebo). | rct | not recorded | Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C. Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels.Journal of Clinical Endocrinology and Metabolism 89(3):1174-1180, 2004 |
| Sixty-nine men aged 60 and over with low or low-normal testosterone took 1 mg daily or placebo for one year. Testosterone rose and estradiol fell as expected, and bone mineral density at the posterior-anterior spine declined in the anastrozole group relative to placebo (p = 0.0014). This is the direct test of the idea that raising testosterone by blocking its conversion is good for male bone, and it came out the other way: the authors concluded that aromatase inhibition does not improve skeletal health in aging men. | rct | not recorded | Burnett-Bowie SA, McKay EA, Lee H, Leder BZ. Effects of aromatase inhibition on bone mineral density and bone turnover in older men with low testosterone levels.Journal of Clinical Endocrinology and Metabolism 94(12):4785-4792, 2009 |
| Two hundred and two healthy men aged 20 to 50 had their own production shut down with goserelin and then received testosterone gel together with anastrozole, so testosterone could be dosed while conversion to estradiol was blocked. Set against the 198 men whose conversion was left intact, this separated the two hormones' jobs. Androgen deficiency accounted for the losses in lean mass, muscle size and strength; estrogen deficiency accounted for the increase in body fat; both contributed to the decline in sexual function. | rct | not recorded | Finkelstein JS, Lee H, Burnett-Bowie SA, Pallais JC, Yu EW, Borges LF, Jones BF, Barry CV, Wulczyn KE, Thomas BJ, Leder BZ. Gonadal steroids and body composition, strength, and sexual function in men.New England Journal of Medicine 369(11):1011-1022, 2013 |
| Twenty-six hypogonadal infertile men were randomized to clomiphene citrate 25 mg daily or anastrozole 1 mg daily for 12 weeks. Both raised testosterone; clomiphene raised it further (571 against 408 ng/dL). Estradiol rose on clomiphene and fell on anastrozole, and only anastrozole significantly raised the testosterone-to-estradiol ratio. Neither arm changed semen parameters or patient-reported outcomes, so over 12 weeks the hormonal effect did not become a measurable functional one. | rct | not recorded | Helo S, Ellen J, Mechlin C, Feustel P, Grossman M, Ditkoff E, McCullough A. A randomized prospective double-blind comparison trial of clomiphene citrate and anastrozole in raising testosterone in hypogonadal infertile men.Journal of Sexual Medicine 12(8):1761-1769, 2015 |
| Men running testosterone typically take 0.25 to 0.5 mg two or three times a week rather than 1 mg daily, and titrate against symptoms or a serum estradiol draw. That is a quarter to half of the oncology tablet per dose, but 0.5 to 1.5 mg a week against 7 mg, so 7 to 21 percent of the oncology exposure. The reported failure mode is over-suppression rather than under-dosing: joint pain, low libido, flat mood and poor sleep appearing several days after an increase, since the two-day half-life means a change takes about a week to settle in blood. Reaching 0.25 mg means quartering a tablet, because no smaller strength is made. | anecdotal | not recorded | community reports aggregated from reddit, MESO-Rx, and similar forumsno study |
How did it get here?
- preclinical1970s
- Aminoglutethimide, an anticonvulsant withdrawn after it caused adrenal insufficiency, is repurposed in breast cancer as a chemical adrenalectomy. Part of its effect turns out to be aromatase inhibition, but it also blocks earlier steps in adrenal steroid synthesis, so patients need hydrocortisone alongside it. What the field goes looking for next is selectivity, not more potency.
- preclinicalearly 1990s
- Development runs at ICI Pharmaceuticals and, after the 1993 demerger, at Zeneca. The compound is ZD1033, a small achiral benzyltriazole that inhibits human placental aromatase with an IC50 of 15 nM. In animals it reaches maximal activity at 0.1 mg/kg by mouth, measured by inhibition of ovulation in rats and by the fall in plasma estradiol in monkeys, and at 30 to 100 times that dose it leaves adrenal corticosteroid synthesis alone and shows no hormonal activity of its own. Those figures come from the Zeneca preclinical pharmacology report (Dukes and colleagues, Journal of Steroid Biochemistry and Molecular Biology 58(4):439-445, 1996).
- first-human1993-1996
- Volunteer and patient studies fix the dose. In healthy postmenopausal volunteers, 0.5, 1 and 3 mg daily all suppress serum estradiol by roughly 80 percent. In patients, 1 mg blocks whole-body aromatization by 96.7 percent against 98.1 percent for a dose ten times larger; that crossover study (Geisler and colleagues, British Journal of Cancer 74(8):1286-1291) was published in 1996, after the December 1995 approval, so it confirmed the chosen dose rather than selected it. Above 1 mg the curve is flat, and 1 mg is still the only strength ever brought to market.
- clinical-adoption1995
- The FDA approves Arimidex on 27 December 1995 (NDA 020541), for advanced breast cancer progressing after tamoxifen. The approved population is postmenopausal women. There has never been an approved indication in men, and there is none today.
- clinical-adoption2002-2014
- The ATAC trial reports in 2002 and anastrozole displaces tamoxifen as adjuvant therapy for postmenopausal women with hormone-receptor-positive disease. In 2014 the IBIS-II prevention trial reports in the Lancet (383(9922):1041-1048) that 1 mg daily for five years cut breast cancer incidence in high-risk postmenopausal women from 85 cases among 1944 on placebo to 40 among 1920 on anastrozole, moving the drug from treatment into prevention.
- grey-marketlate 1990s onward
- Men taking testosterone adopt anastrozole to hold estradiol down, at fractions of the oncology dose. Two channels supply it. One is the ordinary pharmacy: prescribing a drug off-label is legal, and the first generic tablets, approved on 28 June 2010, a day on which the FDA approval database records a dozen abbreviated applications clearing at once, made those prescriptions cheap. The other is bulk powder dissolved in solvent and sold by the milliliter. The dosing conventions come from forums, worked out against symptoms and lab draws. The randomized evidence in men covers hypogonadal or elderly men on replacement doses or on nothing at all, which is not the population using it.
How is it made?
Anastrozole is not a steroid and is not made from one. Production has three stages.
1. Building the core. Manufacture starts from a benzene ring carrying nitrile-tipped arms at the 1 and 3 positions and a methyl group at the 5 position, and methylates the arms to give the tetramethyl pattern in its chemical name. That 5-position methyl is a handle for the next stage, not part of the finished drug. No carbon in anastrozole carries four different groups, so it is achiral: no mirror image to separate, no second form with different activity.
2. Attaching the triazole. The 5-methyl group is converted into a reactive site by benzylic bromination, then displaced with 1,2,4-triazole. That five-membered ring is the working end of the drug: one of its nitrogen atoms coordinates the iron at the center of aromatase's heme group, and holding that position is what stops the enzyme. The triazole can attach through either of two nitrogens, so the reaction also yields an inactive isomer; separating the two is the main purification burden.
3. Making the tablet. Each tablet holds 1 mg of drug, blended with lactose, a binder, a disintegrant and a lubricant, then coated. One milligram is a small quantity of powder, so milling and blending decide how much drug a tablet contains, and content uniformity testing on every batch proves they worked. What varies outside regulated manufacturing is not the synthetic route, which is short and ordinary, but the blend uniformity and whether it was ever measured.
Worth knowing
Anastrozole has only ever been sold in one strength. Every marketed tablet contains 1 mg, and the label's dose instruction is one line: one 1 mg tablet once a day, with or without food, with no adjustment for age or for kidney impairment. Community practice starts around a quarter of that, a dose that has never existed as a product, so it is reached by splitting a tablet that was manufactured and film coated only as a whole 1 mg unit.
Arimidex (anastrozole) tablets prescribing information, DESCRIPTION, DOSAGE FORMS AND STRENGTHS and DOSAGE AND ADMINISTRATION sections.ANI Pharmaceuticals, US FDA label, NDA 020541
The molecule is symmetric by design, and it is also achiral: no carbon in it carries four different groups, so there is no enantiomer to resolve and none to behave differently in the body. It inhibits human placental aromatase in vitro with an IC50 of 15 nM, and at 30 to 100 times its effective animal dose it left adrenal corticosteroid synthesis untouched and showed no hormonal activity of its own in the standard assays (estrogenic, anti-estrogenic, androgenic, anti-androgenic, progestogenic, glucocorticoid, antiglucocorticoid and mineralocorticoid).
Dukes M, Edwards PN, Large M, Smith IK, Boyle T. The preclinical pharmacology of Arimidex (anastrozole; ZD1033), a potent, selective aromatase inhibitor.Journal of Steroid Biochemistry and Molecular Biology 58(4):439-445, 1996
Aromatase is the only enzyme in vertebrates known to make estrogens, and it makes them the hard way: three sequential oxidation steps, each consuming one molecule of oxygen and one of NADPH. The first two hydroxylate the steroid's C19 methyl group and the third removes it, turning the A-ring aromatic. The same enzyme converts androstenedione to estrone, testosterone to 17-beta-estradiol and 16-alpha-hydroxytestosterone to estriol. Its crystal structure was not solved until 2009, after decades in which the enzyme's shape stayed unknown, because it sits anchored in the endoplasmic reticulum membrane.
Ghosh D, Griswold J, Erman M, Pangborn W. Structural basis for androgen specificity and oestrogen synthesis in human aromatase.Nature 457(7226):219-223, 2009
Written and reviewed by Evan Marlow, developer of DosePlot · Updated 2026-08-27
Not medical advice. DosePlot is an informational tool, not a healthcare provider, and using it creates no provider-patient relationship. Do not start, stop, or change any protocol without the approval of a licensed healthcare professional.
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