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Head-to-head

Anastrozole vs Enclomiphene

Two prescription drugs used off-label by men to raise testosterone through completely different mechanisms — one blocks estrogen conversion, the other stimulates the brain's own signal to the testes.

By Julian RothResearch & dataUpdated October 2026

Short answer

Anastrozole has FDA approval and enclomiphene does not, which is the main thing separating them. Anastrozole suits a reader who puts weight on FDA approval, though that approval does not cover every use it is marketed for, while enclomiphene is marketed for raising testosterone and preserving fertility. On the evidence, anastrozole has approval-level evidence and enclomiphene has human clinical data.

Anastrozole

Arimidex

FDA-approved

An approved aromatase inhibitor for breast cancer, used off-label in men to raise testosterone by blocking its conversion to estrogen — a real endocrine effect, but off-label use in men who are not on TRT risks pushing estrogen too low, with real bone-density and lipid consequences.

Full Anastrozole evidence review

Enclomiphene

Clinical data

Randomized Phase III data: restores a man's own testosterone while preserving sperm — but never FDA-approved for men, and compounded.

Full Enclomiphene evidence review

Anastrozole vs Enclomiphene: head to head

FDA status / approved use

Anastrozole

FDA-approved (Arimidex) for hormone-receptor-positive breast cancer in women; use in men is off-label

Enclomiphene

Not FDA-approved; its application for male hypogonadism was not approved, so use is off-label
Marketed for

Anastrozole

Breast cancer (approved); off-label testosterone/estrogen management in men

Enclomiphene

Raising testosterone, preserving fertility
Outcome areas

Anastrozole

Testosterone / male hormones; Joint / bone health

Enclomiphene

Testosterone / male hormones
Evidence grade

Anastrozole

FDA-approved

Enclomiphene

Clinical data
How it works

Anastrozole

Blocks aromatase, the enzyme that converts testosterone into estradiol

Enclomiphene

Blocks estrogen feedback so LH, FSH and the body's own testosterone rise
Route and dosing

Anastrozole

Taken daily in trials of older men

Enclomiphene

Oral medication
Headline human result

Anastrozole

Raised testosterone but gave no meaningful improvement in sexual function, mood, or quality of life in a 2009 placebo-controlled trial

Enclomiphene

Testosterone up +7.50 nmol/L in a 2023 meta-analysis of 7 studies (292 men); clomiphene raised it more
Strongest evidence

Anastrozole

Aromatase inhibition in elderly men RCT, JCEM 2004Anastrozole evidence reviewPubMed 15001605

Enclomiphene

Phase III RCT, BJU Int 2016Enclomiphene evidence reviewPubMed 26496621
Key safety signal

Anastrozole

Lowers spinal bone mineral density and raises bone-resorption markers in men

Enclomiphene

No long-term data on bone, heart or mortality outcomes
How it is obtained

Anastrozole

Prescription drug

Enclomiphene

Prescribed off-label and dispensed by compounding pharmacies

marks a row where the two differ. “Not established” marks a cell the available evidence does not answer. Evidence grades come from our evidence matrix, which grades each molecule on the human data for the use it is marketed for.

FDA-approved:
Approved by the FDA for a defined indication, on the strength of pivotal human trials.
Clinical data:
Tested in humans — but investigational, discontinued, or proven only on a surrogate marker (not the marketed outcome).

Our verdict

Enclomiphene has real Phase 3 data specifically for its off-label use: it raises a man's own testosterone while preserving sperm production and fertility, though it has never been FDA-approved for men and is compounded. Anastrozole is FDA-approved, but for breast cancer — its off-label male use lowers estrogen by blocking aromatase, which can raise free testosterone indirectly but risks pushing estrogen too low, with real consequences for bone density and lipids. They aren't interchangeable: enclomiphene raises testosterone directly, anastrozole only reshapes the testosterone-to-estrogen ratio.

Anastrozole fits if

Estrogen is already elevated (common on TRT) and the goal is rebalancing the ratio, ideally with bloodwork guiding the dose to avoid crashing estrogen.

Enclomiphene fits if

Raising your own testosterone while preserving fertility is the actual goal — this is the drug with trial data for exactly that use, not a repurposed cancer drug.

Anastrozole vs Enclomiphene: common questions

Is anastrozole FDA-approved but enclomiphene not?
Yes. Anastrozole is FDA-approved (Arimidex) for hormone-receptor-positive breast cancer in women; use in men is off-label. Enclomiphene is not FDA-approved; its application for male hypogonadism was not approved, so use is off-label.
Which has stronger human evidence, anastrozole or enclomiphene?
Anastrozole. It has approval-level evidence (key source: Aromatase inhibition in elderly men RCT, JCEM 2004), while enclomiphene has human clinical data (key source: Phase III RCT, BJU Int 2016).
What are the main safety concerns with anastrozole and enclomiphene?
Anastrozole lowers spinal bone mineral density and raises bone-resorption markers in men. Enclomiphene has no long-term data on bone, heart or mortality outcomes.

Key studies behind each

Anastrozole

  1. Leder BZ, Rohrer JL, Rubin SD, et al. (2004). Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. J Clin Endocrinol Metab. PubMed 15001605
  2. Burnett-Bowie SA, Roupenian KC, Dere ME, et al. (2009). Effects of aromatase inhibition in hypogonadal older men: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol (Oxf). PubMed 18616708
  3. Burnett-Bowie SA, McKay EA, Lee H, et al. (2009). Effects of aromatase inhibition on bone mineral density and bone turnover in older men with low testosterone levels. J Clin Endocrinol Metab. PubMed 19820017
  4. Finkelstein JS, Yu EW, Burnett-Bowie SA, et al. (2013). Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. PubMed 24350954

Enclomiphene

  1. Kaminetsky J, Werner M, Fontenot G, Wiehle RD. (2013). Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel. J Sex Med. PubMed 23530575
  2. Wiehle R, Cunningham GR, Pitteloud N, et al. (2013). Testosterone restoration by enclomiphene citrate in men with secondary hypogonadism: pharmacodynamics and pharmacokinetics. BJU Int. PubMed 23875626
  3. Wiehle RD, Fontenot GK, Wike J, et al. (2014). Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone. Fertil Steril. PubMed 25044085
  4. Kim ED, McCullough A, Kaminetsky J. (2016). Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement. BJU Int. PubMed 26496621

The full evidence reviews

Where to get it

Where to get testosterone therapy

Testosterone and hormone-optimization telehealth services with clinician oversight and lab work. Confirm current pricing and lab requirements — and whether Anastrozole fits your case — with the provider.

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