Letrozole

updated

Letrozole is an FDA-approved aromatase inhibitor for hormone receptor-positive breast cancer in postmenopausal women (FEMARA, 1997), and the label carries no indication in men. In healthy men it lowered estradiol by 46% to 62% and raised testosterone, but in 42 obese men a rise in testosterone from 8.6 to 21.5 nmol/L produced no significant somatic or psychological effects. Two PubMed searches on 10 October 2026 found no controlled trial of letrozole for gynecomastia or water retention in men, and the only trial in steroid users found has no abstract.

Aromatase inhibitor

  • FDA first approved FEMARA under NDA 020726 on 25 July 1997 for postmenopausal women only; the label carries no indication in men.
  • In BIG 1-98 (over 8,000 postmenopausal women), disease-free survival favored letrozole over tamoxifen (HR 0.87, 95% CI 0.76 to 0.99) at a median 73 months in the monotherapy-arms analysis.
  • In 10 young and 10 elderly healthy men, letrozole lowered estradiol by 46% and 62% and raised LH by 339% and 323%.
  • In 42 obese men with low testosterone, testosterone rose from 8.6 to 21.5 nmol/L with no significant effect on psychological, body composition, exercise capacity, glucose, lipid or bone endpoints.
  • In 296 men with spermatogenic failure, decreased libido was reported by 12.2% on letrozole versus 5.4% on control.
  • A European guideline does not recommend aromatase inhibitors for gynecomastia in general, and 34.9% of 63 seized post-cycle therapy products lacked the declared active ingredient.

What is letrozole approved to do?

FDA approved FEMARA (letrozole) on 25 July 1997. It is labeled only for postmenopausal women with breast cancer, and the label carries no indication in men.

The FEMARA label covers three uses in postmenopausal women: adjuvant treatment of hormone receptor-positive early breast cancer, extended adjuvant treatment after 5 years of tamoxifen, and first and second-line treatment of hormone receptor-positive or unknown advanced breast cancer. The label version used here took effect on 11 June 2026, and it carries no indication in men.

FDA first approved FEMARA under NDA 020726 on 25 July 1997. The sponsor on the openFDA record is Novartis. Approvals outside the United States are not covered here.

Letrozole is C17H11N5 (285.30 g/mol, CAS 112809-51-5, PubChem CID 3902). FEMARA and the generics contain letrozole itself, not a salt, so label doses are letrozole.

FEMARA label, version effective 11 June 2026: indication, estrogen suppression, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. FEMARA (letrozole) film-coated oral tablets, prescribing information, label version effective 11 June 2026. Set ID 82b77d74-085f-45ac-a7dd-1f5c038bf406.

The label approves FEMARA only for postmenopausal women: adjuvant treatment of hormone receptor-positive early breast cancer, extended adjuvant treatment after 5 years of tamoxifen, and first and second-line treatment of hormone receptor-positive or unknown advanced breast cancer. The label carries no indication in men. In postmenopausal women with advanced breast cancer, daily doses of 0.1 to 5 mg suppressed plasma estradiol, estrone and estrone sulfate by 75 to 95% from baseline, with maximal suppression within 2 to 3 days, and plasma LH and FSH were not affected in those patients. Letrozole is rapidly and completely absorbed, food does not affect absorption, the terminal elimination half-life is about 2 days, and steady state is reached in 2 to 6 weeks of daily dosing. In BIG 1-98 (NCT00004205, over 8,000 women), the monotherapy-arms analysis at a median 73 months found disease-free survival favored letrozole over tamoxifen (HR 0.87, 95% CI 0.76 to 0.99, P = 0.03; 445 versus 500 events among 2,463 and 2,459 women). Warnings cover lower bone mineral density (median lumbar spine change of -4.1% with letrozole versus +0.3% with tamoxifen at 24 months in a 263-woman safety study), fractures (14.7% versus 11.4% with tamoxifen in BIG 1-98 at median 96 months), hypercholesterolemia (52.3% versus 28.6%), fatigue, dizziness, somnolence and embryo-fetal toxicity. Safety and effectiveness in pediatric patients have not been established, and, based on studies in male animals, FEMARA may impair fertility in males of reproductive potential.

Participants / model
Postmenopausal women with breast cancer; label PK participants
Treatment
FEMARA 2.5 mg film-coated oral tablets
Follow-up
Label version effective 11 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The estrogen-suppression figures come from postmenopausal women and should not be transferred to men. The label carries no indication in men.

Read the original source
Drugs@FDA: FEMARA approved 25 July 1997

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 020726 (FEMARA). Dates read from the openFDA Drugs@FDA record.

FDA first approved FEMARA under NDA 020726 on 25 July 1997. The sponsor on the openFDA record is Novartis.

Participants / model
Not a clinical population
Treatment
Drug application
Follow-up
Approved 1997
Study design
FDA application record
Funding
not stated in the source

This record gives the approval date and sponsor. Indications come from the product label.

Read the original source
PubChem: letrozole identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 3902 (letrozole).

Letrozole: PubChem CID 3902, C17H11N5, 285.30 g/mol, CAS 112809-51-5. FEMARA and the generics contain letrozole itself, not a salt.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

What did the large breast cancer trial find?

In BIG 1-98, which enrolled over 8,000 postmenopausal women, disease-free survival favored letrozole over tamoxifen at a median 73 months in the monotherapy-arms analysis (HR 0.87, 95% CI 0.76 to 0.99).

In the monotherapy-arms analysis of BIG 1-98 (NCT00004205), at a median 73 months, disease-free survival favored letrozole over tamoxifen (HR 0.87, 95% CI 0.76 to 0.99, P = 0.03). There were 445 events among 2,463 women on letrozole and 500 among 2,459 on tamoxifen.

The trial was in postmenopausal women with breast cancer, so none of these results describe men or steroid-cycle use.

FEMARA label, version effective 11 June 2026: indication, estrogen suppression, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. FEMARA (letrozole) film-coated oral tablets, prescribing information, label version effective 11 June 2026. Set ID 82b77d74-085f-45ac-a7dd-1f5c038bf406.

The label approves FEMARA only for postmenopausal women: adjuvant treatment of hormone receptor-positive early breast cancer, extended adjuvant treatment after 5 years of tamoxifen, and first and second-line treatment of hormone receptor-positive or unknown advanced breast cancer. The label carries no indication in men. In postmenopausal women with advanced breast cancer, daily doses of 0.1 to 5 mg suppressed plasma estradiol, estrone and estrone sulfate by 75 to 95% from baseline, with maximal suppression within 2 to 3 days, and plasma LH and FSH were not affected in those patients. Letrozole is rapidly and completely absorbed, food does not affect absorption, the terminal elimination half-life is about 2 days, and steady state is reached in 2 to 6 weeks of daily dosing. In BIG 1-98 (NCT00004205, over 8,000 women), the monotherapy-arms analysis at a median 73 months found disease-free survival favored letrozole over tamoxifen (HR 0.87, 95% CI 0.76 to 0.99, P = 0.03; 445 versus 500 events among 2,463 and 2,459 women). Warnings cover lower bone mineral density (median lumbar spine change of -4.1% with letrozole versus +0.3% with tamoxifen at 24 months in a 263-woman safety study), fractures (14.7% versus 11.4% with tamoxifen in BIG 1-98 at median 96 months), hypercholesterolemia (52.3% versus 28.6%), fatigue, dizziness, somnolence and embryo-fetal toxicity. Safety and effectiveness in pediatric patients have not been established, and, based on studies in male animals, FEMARA may impair fertility in males of reproductive potential.

Participants / model
Postmenopausal women with breast cancer; label PK participants
Treatment
FEMARA 2.5 mg film-coated oral tablets
Follow-up
Label version effective 11 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The estrogen-suppression figures come from postmenopausal women and should not be transferred to men. The label carries no indication in men.

Read the original source

What happened to hormones and the body in men given letrozole?

Letrozole lowered estradiol and raised LH and testosterone in healthy men. In 42 obese men with low testosterone, a rise from 8.6 to 21.5 nmol/L produced no significant psychological, body composition, exercise, glucose, lipid or bone effects, and infertile men on letrozole reported more decreased libido.

In 10 healthy young men and 10 healthy elderly men given placebo and then letrozole 2.5 mg daily for 28 days (with a 2-week washout between), letrozole lowered estradiol by 46% in the young and 62% in the elderly, raised LH by 339% and 323%, and raised testosterone by 146% and 99%. This was a hormone study, with no gynecomastia, body composition or symptom endpoint.

In a double-blind placebo-controlled 6-month trial in 42 obese men (BMI over 35 kg/m2, total testosterone under 10 nmol/L), letrozole was dose-escalated monthly toward a testosterone target of 20 nmol/L. Estradiol fell from 119.1 to 59.2 pmol/L, LH rose from 3.3 to 8.8 U/L and total testosterone rose from 8.6 to 21.5 nmol/L, but no significant effects were seen on the predefined psychological, body composition, exercise capacity, glucose, lipid or bone endpoints. The authors concluded that a marked testosterone rise did not produce somatic or psychological effects in these men.

In a 2026 multicenter randomized trial in 296 men with spermatogenic failure (73.6% with nonobstructive azoospermia, mean age 30.2 years), letrozole 2.5 mg daily plus vitamins C and E for 3 months was compared with vitamins alone. The WHO sperm concentration category upgrade rate was 14.3% (21 of 147) versus 5.4% (8 of 149) (risk difference 9.2%, 95% CI 2.5 to 15.8%, P = 0.01), with no significant between-group difference in semen parameters. Letrozole raised gonadotropins and testosterone and lowered estradiol. Decreased libido was reported by 18 men (12.2%) on letrozole versus 8 (5.4%) on control (P = 0.04). The trial was open-label with assessor blinding, and the men were infertile, not steroid users.

20 healthy men, 28 days: estradiol down, LH and testosterone up

Human study

T'Sjoen GG et al. J Clin Endocrinol Metab. 2005;90(10):5717-22. PMID 16046582.

Letrozole lowered estradiol by 46% in the young men and 62% in the elderly men, raised LH by 339% and 323%, and raised testosterone by 146% and 99%. The endpoints were free estradiol, LH, FSH, free testosterone, SHBG and GnRH response. There was no gynecomastia, body composition or symptom endpoint.

Participants / model
10 healthy young men and 10 healthy elderly men
Treatment
Oral letrozole 2.5 mg daily for 28 days, versus placebo, with a 2-week washout between
Follow-up
28 days of letrozole
Study design
Comparative intervention study: placebo, then letrozole
Funding
not stated in the source

A hormone study. It shows that letrozole lowers estradiol in healthy men and that testosterone and LH rise sharply, and it says nothing about gynecomastia or symptoms.

Read the original source
42 obese men, 6 months: testosterone up from 8.6 to 21.5 nmol/L, no somatic effect

Randomized controlled trial

Loves S et al. Eur J Endocrinol. 2013;169(5):705-14. PMID 23949882.

Estradiol fell from 119.1 to 59.2 pmol/L, LH rose from 3.3 to 8.8 U/L and total testosterone rose from 8.6 to 21.5 nmol/L, but no significant effects were seen on the predefined psychological, body composition, exercise capacity, glucose, lipid or bone endpoints. The authors concluded that a marked testosterone rise did not produce somatic or psychological effects in these men.

Participants / model
42 obese men (BMI over 35 kg/m2) with total testosterone under 10 nmol/L
Treatment
Oral letrozole dose-escalated monthly toward a testosterone target of 20 nmol/L, or placebo
Follow-up
6 months
Study design
Double-blind placebo-controlled randomized trial
Funding
not stated in the source

Obese men with low testosterone, not steroid users. Endpoints were psychological function, body composition, exercise capacity, glucose, lipids and bone metabolism.

Read the original source
296 infertile men, 3 months: sperm category upgrade 14.3% versus 5.4%, decreased libido 12.2% versus 5.4%

Randomized controlled trial

Sun Y et al. JAMA Netw Open. 2026;9(6):e2618422. PMID 42313386.

The WHO sperm concentration category upgrade rate was 14.3% (21 of 147) versus 5.4% (8 of 149) (risk difference 9.2%, 95% CI 2.5 to 15.8%, P = 0.01), with no significant between-group difference in semen parameters. Letrozole raised gonadotropins and testosterone and lowered estradiol. Decreased libido was reported by 18 men (12.2%) on letrozole versus 8 (5.4%) on control (P = 0.04).

Participants / model
296 men with spermatogenic failure (73.6% with nonobstructive azoospermia), mean age 30.2 years
Treatment
Oral letrozole 2.5 mg daily plus vitamins C and E, or vitamins alone
Follow-up
3 months
Study design
2026 multicenter randomized trial, open-label with assessor blinding
Funding
not stated in the source

The men were infertile, not steroid users. Endpoints were the WHO sperm concentration category upgrade, semen parameters, reproductive hormones and adverse events.

Read the original source

Does letrozole treat or prevent gynecomastia?

No trial found tests it in men. A narrative review of aromatase inhibitors in children and adolescents concluded they are probably ineffective in gynecomastia, and a European guideline does not recommend aromatase inhibitors for gynecomastia in general.

A narrative review of aromatase inhibitors (letrozole and anastrozole) in children and adolescents concluded they are probably ineffective in gynecomastia. It found they appear effective for raising adult height in boys with short stature or pubertal delay, with safety concerns that include vertebral deformities, lower HDL cholesterol and higher erythrocytosis. This is pediatric evidence, not evidence in adult steroid users.

The European Academy of Andrology guideline does not recommend selective estrogen receptor modulators, aromatase inhibitors or non-aromatizable androgens for gynecomastia in general (recommendation 14, strong recommendation, low-quality evidence). It recommends watchful waiting after a substance associated with gynecomastia is stopped, and states that in more than 90% of cases pubertal gynecomastia resolves spontaneously within 24 months. The abstract does not name letrozole.

Narrative review: aromatase inhibitors probably ineffective in gynecomastia in the young

Human study

Wit JM et al. Nat Rev Endocrinol. 2011;8(3):135-47. PMID 22024975.

The review concluded that aromatase inhibitors are probably ineffective in gynecomastia. It also found they appear effective for raising adult height in boys with short stature or pubertal delay, with safety concerns that include vertebral deformities, lower HDL cholesterol and higher erythrocytosis.

Participants / model
Children and adolescents (narrative review)
Treatment
Oral letrozole and anastrozole
Follow-up
Not applicable
Study design
Narrative review
Funding
not stated in the source

Pediatric evidence, not adult steroid users.

Read the original source
European Academy of Andrology guideline: no aromatase inhibitors for gynecomastia in general

Human study

Kanakis GA et al. Andrology. 2019;7(6):778-793. PMID 31099174.

The guideline does not recommend selective estrogen receptor modulators, aromatase inhibitors or non-aromatizable androgens for gynecomastia in general (recommendation 14, strong, low-quality evidence). It recommends watchful waiting after a substance associated with gynecomastia is stopped, and states that in more than 90% of cases pubertal gynecomastia resolves spontaneously within 24 months. The abstract does not name letrozole.

Participants / model
Boys and men with gynecomastia (guideline scope)
Treatment
Not drug-specific
Follow-up
Not applicable
Study design
Clinical practice guideline (GRADE)
Funding
not stated in the source

A recommendation for gynecomastia in general. It is not specific to letrozole.

Read the original source

Is letrozole a way to control estrogen on a steroid cycle?

No study found tests it. Two PubMed searches on 10 October 2026 found no controlled trial of letrozole for gynecomastia or water retention in men, and the only trial in former steroid users found has no abstract.

Sellers describe letrozole, like anastrozole and exemestane, as an aromatase inhibitor that steroid users take for estrogen control and to prevent or treat gynecomastia.

A PubMed search on 10 October 2026 for letrozole with anabolic steroid, anabolic-androgenic or bodybuilding terms returned 8 records: a rodent neurogenesis review, three drug-detection method papers (urine and hair), a case report of rhabdomyolysis with dexmethylphenidate and an aromatase inhibitor, the forum and seized-product analyses below, and a former-user trial described below. Apart from that trial, none tested letrozole for estrogen control, gynecomastia or water retention in men using steroids. A second search for letrozole with gynecomastia or water or fluid retention in men or boys returned 8 records: three reviews, two mouse studies, a single-child Peutz-Jeghers case report, an aromatase excess syndrome family report and a urine detection paper. None was a controlled trial of letrozole for gynecomastia or water retention in men.

A randomized clinical trial titled Effects of letrozole therapy in former users of anabolic steroids was published in J Intern Med in 2025 (volume 297, pages 113 to 116) by a Copenhagen group. No abstract is posted on PubMed, Europe PMC or Crossref, so its design, dose, size and results are not described here, and nothing on this page rests on it. Its title places the question in former users (post-cycle), not in men on cycle. A registered trial from the same hospital, LUCAS (NCT05205837), tested letrozole plus hCG against placebo in men aged 18 to 50 with hypogonadism from illicit anabolic steroid use. It was terminated with 8 participants enrolled and has no posted results, and whether the two records describe the same study is not established.

An analysis of 1,792 posts on a French bodybuilding forum (2013 to 2019), by men with a mean age of 28.2 years, found aromatase inhibitors used mainly to fight androgen aromatization. Among five drugs analyzed, the median letrozole course was 30 days at a mean 2 mg a day, and the drugs were mainly bought online. This records how the drug is used, not whether it works. The forum mean is close to the dose given in the healthy-men study above, and no study found tests lower or intermittent doses in men.

Poland's official medicines control laboratory tested 63 seized illegal post-cycle therapy products (2020 to 2024) labeled as SERMs, aromatase inhibitors (anastrozole, letrozole, exemestane) or other agents such as hCG and cabergoline. The declared active ingredient was present in 65.1% and absent in 34.9% (20.6% with no active ingredient and 14.3% with other undeclared ingredients), and 6.4% contained an extra undeclared ingredient. Per-drug results are not given in the abstract, so no letrozole-specific purity figure exists and a gray-market product may not be the drug tested in the studies on this page.

PubMed searches, 10 October 2026: 8 records and 8 records, none testing the supplier claim

PubMed search record

PubMed searches run on 10 October 2026: (1) letrozole[tiab] AND (anabolic steroid*[tiab] OR anabolic-androgenic[tiab] OR anabolic androgenic[tiab] OR bodybuild*[tiab]); (2) letrozole[tiab] AND (gynecomastia[tiab] OR gynaecomastia[tiab] OR "water retention"[tiab] OR "fluid retention"[tiab]) AND (men[tiab] OR male*[tiab] OR boys[tiab]). 8 and 8 records returned.

The first search returned 8 records: a rodent neurogenesis review, three drug-detection method papers (urine and hair), a case report of rhabdomyolysis with dexmethylphenidate and an aromatase inhibitor, the forum and seized-product analyses described on this page, and the former-user trial whose abstract is not available. Apart from that trial, none tested letrozole for estrogen control, gynecomastia or water retention in men using steroids. The second search returned 8 records: three reviews, two mouse studies, a single-child Peutz-Jeghers case report, an aromatase excess syndrome family report and a urine detection paper. None was a controlled trial of letrozole for gynecomastia or water retention in men.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
J Intern Med 2025 trial in former steroid users: no abstract on PubMed

Human study

Rasmussen JJ et al. J Intern Med. 2025;297(1):113-116. PMID 39578999.

A randomized clinical trial titled Effects of letrozole therapy in former users of anabolic steroids was published in J Intern Med in 2025 (volume 297, pages 113 to 116) by a Copenhagen group. PubMed, Europe PMC and Crossref hold no abstract for it, so its design, dose, size and results are not described here. A registered trial from the same hospital, LUCAS (NCT05205837), tested letrozole plus intramuscular hCG against placebo in men aged 18 to 50 with hypogonadism from illicit anabolic steroid use. It was terminated with 8 participants enrolled and has no posted results. Whether the two records describe the same study is not established.

Participants / model
Former anabolic steroid users (title only); the registry record lists men aged 18 to 50 with steroid-induced hypogonadism
Treatment
Oral letrozole, details not described; the registry record lists letrozole plus intramuscular hCG
Follow-up
not stated in the source
Study design
Randomized clinical trial by title; abstract not available
Funding
not stated in the source

Its title places the question in former users (post-cycle), not in men on cycle. Nothing about its results is described on this page.

Read the original source
1,792 forum posts, 2013 to 2019: median letrozole course 30 days at a mean 2 mg a day

Human study

Rochoy M et al. Therapie. 2022;77(6):683-691. PMID 35660259.

Aromatase inhibitors were used mainly to fight androgen aromatization. Among five drugs analyzed, the median letrozole course was 30 days at a mean 2 mg a day, and the drugs were mainly bought online. The 62 adverse drug reactions attributed to aromatase inhibitors as a group were mainly acne, musculoskeletal, mood and reproductive disorders, and impaired quality of life was described in 26% of aromatase inhibitor posts.

Participants / model
Men posting on one anabolic steroid forum, mean age 28.2 years
Treatment
Self-sourced oral letrozole, self-reported doses
Follow-up
Posts from 2013 to 2019
Study design
Observational analysis of 1,792 forum posts
Funding
not stated in the source

This records how the drug is used, not whether it works. Doses and reactions are self-reported, and the reactions are attributed to aromatase inhibitors as a group.

Read the original source
63 seized products, 2020 to 2024: 34.9% lacked the declared ingredient

Regulatory record

Blazewicz A et al. Front Chem. 2025;13:1536858. PMID 40177353.

Poland's official medicines control laboratory tested 63 seized illegal post-cycle therapy products labeled as SERMs, aromatase inhibitors (anastrozole, letrozole, exemestane) or other agents such as hCG and cabergoline. The declared active ingredient was present in 65.1% and absent in 34.9% (reported as 20.6% with no active ingredient and 14.3% with other undeclared ingredients), and 6.4% contained an extra undeclared ingredient. Per-drug results are not given in the abstract.

Participants / model
Seized products, not a clinical population (63 of 601 samples)
Treatment
Illegal post-cycle therapy products as seized
Follow-up
Products seized 2020 to 2024
Study design
Official laboratory product analysis
Funding
not stated in the source

No letrozole-specific purity figure exists in this record. A gray-market product may not be the drug tested in the studies on this page.

Read the original source

How does letrozole work, and what does the body do with it?

Letrozole is an aromatase inhibitor that lowers estrogen. The label reports 75 to 95% lower estradiol, estrone and estrone sulfate in postmenopausal women with advanced breast cancer, and in healthy men estradiol fell by 46% to 62% while LH and testosterone rose sharply. The terminal half-life is about 2 days.

In postmenopausal women with advanced breast cancer, the label reports that daily doses of 0.1 to 5 mg suppressed plasma estradiol, estrone and estrone sulfate by 75 to 95% from baseline, with maximal suppression within 2 to 3 days. The label says plasma LH and FSH were not affected in those patients.

Those figures come from postmenopausal women and should not be transferred to men. In healthy men the same drug lowered estradiol by 46% in young and 62% in elderly men and raised LH by 339% and 323%, so LH did not stay flat. Testosterone rose by 146% and 99%. The estrogen fall is real in men, and the outcome trials above did not show a somatic or psychological benefit from the hormone change.

In the label, letrozole is rapidly and completely absorbed, and food does not affect absorption. The terminal elimination half-life is about 2 days, and steady state is reached in 2 to 6 weeks of daily dosing. Baseline Tmax is not given in the sources reviewed, and no PK figures for men appear in them.

FEMARA label, version effective 11 June 2026: indication, estrogen suppression, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. FEMARA (letrozole) film-coated oral tablets, prescribing information, label version effective 11 June 2026. Set ID 82b77d74-085f-45ac-a7dd-1f5c038bf406.

The label approves FEMARA only for postmenopausal women: adjuvant treatment of hormone receptor-positive early breast cancer, extended adjuvant treatment after 5 years of tamoxifen, and first and second-line treatment of hormone receptor-positive or unknown advanced breast cancer. The label carries no indication in men. In postmenopausal women with advanced breast cancer, daily doses of 0.1 to 5 mg suppressed plasma estradiol, estrone and estrone sulfate by 75 to 95% from baseline, with maximal suppression within 2 to 3 days, and plasma LH and FSH were not affected in those patients. Letrozole is rapidly and completely absorbed, food does not affect absorption, the terminal elimination half-life is about 2 days, and steady state is reached in 2 to 6 weeks of daily dosing. In BIG 1-98 (NCT00004205, over 8,000 women), the monotherapy-arms analysis at a median 73 months found disease-free survival favored letrozole over tamoxifen (HR 0.87, 95% CI 0.76 to 0.99, P = 0.03; 445 versus 500 events among 2,463 and 2,459 women). Warnings cover lower bone mineral density (median lumbar spine change of -4.1% with letrozole versus +0.3% with tamoxifen at 24 months in a 263-woman safety study), fractures (14.7% versus 11.4% with tamoxifen in BIG 1-98 at median 96 months), hypercholesterolemia (52.3% versus 28.6%), fatigue, dizziness, somnolence and embryo-fetal toxicity. Safety and effectiveness in pediatric patients have not been established, and, based on studies in male animals, FEMARA may impair fertility in males of reproductive potential.

Participants / model
Postmenopausal women with breast cancer; label PK participants
Treatment
FEMARA 2.5 mg film-coated oral tablets
Follow-up
Label version effective 11 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The estrogen-suppression figures come from postmenopausal women and should not be transferred to men. The label carries no indication in men.

Read the original source
20 healthy men, 28 days: estradiol down, LH and testosterone up

Human study

T'Sjoen GG et al. J Clin Endocrinol Metab. 2005;90(10):5717-22. PMID 16046582.

Letrozole lowered estradiol by 46% in the young men and 62% in the elderly men, raised LH by 339% and 323%, and raised testosterone by 146% and 99%. The endpoints were free estradiol, LH, FSH, free testosterone, SHBG and GnRH response. There was no gynecomastia, body composition or symptom endpoint.

Participants / model
10 healthy young men and 10 healthy elderly men
Treatment
Oral letrozole 2.5 mg daily for 28 days, versus placebo, with a 2-week washout between
Follow-up
28 days of letrozole
Study design
Comparative intervention study: placebo, then letrozole
Funding
not stated in the source

A hormone study. It shows that letrozole lowers estradiol in healthy men and that testosterone and LH rise sharply, and it says nothing about gynecomastia or symptoms.

Read the original source
42 obese men, 6 months: testosterone up from 8.6 to 21.5 nmol/L, no somatic effect

Randomized controlled trial

Loves S et al. Eur J Endocrinol. 2013;169(5):705-14. PMID 23949882.

Estradiol fell from 119.1 to 59.2 pmol/L, LH rose from 3.3 to 8.8 U/L and total testosterone rose from 8.6 to 21.5 nmol/L, but no significant effects were seen on the predefined psychological, body composition, exercise capacity, glucose, lipid or bone endpoints. The authors concluded that a marked testosterone rise did not produce somatic or psychological effects in these men.

Participants / model
42 obese men (BMI over 35 kg/m2) with total testosterone under 10 nmol/L
Treatment
Oral letrozole dose-escalated monthly toward a testosterone target of 20 nmol/L, or placebo
Follow-up
6 months
Study design
Double-blind placebo-controlled randomized trial
Funding
not stated in the source

Obese men with low testosterone, not steroid users. Endpoints were psychological function, body composition, exercise capacity, glucose, lipids and bone metabolism.

Read the original source

What risks do the label and the male studies report?

The label warns of lower bone mineral density, fractures, higher cholesterol, fatigue, dizziness, somnolence and embryo-fetal toxicity, and says male animal studies suggest it may impair fertility in males. In men with spermatogenic failure, decreased libido was more common on letrozole (12.2% versus 5.4%), and no fracture or cardiovascular outcome in men was found.

The FEMARA label warns of lower bone mineral density (median lumbar spine change of -4.1% with letrozole versus +0.3% with tamoxifen at 24 months in a 263-woman safety study), fractures (14.7% versus 11.4% with tamoxifen in BIG 1-98 at median 96 months), hypercholesterolemia (52.3% versus 28.6%), fatigue, dizziness, somnolence and embryo-fetal toxicity. These warnings come from women with breast cancer.

The label states that safety and effectiveness in pediatric patients have not been established. It also states that, based on studies in male animals, FEMARA may impair fertility in males of reproductive potential.

In men, decreased libido was reported by 12.2% on letrozole versus 5.4% on control among 296 men with spermatogenic failure. The pediatric review lists vertebral deformities, lower HDL cholesterol and higher erythrocytosis among safety concerns. No fracture or cardiovascular outcome in men was found.

Users on the French forum described 62 adverse drug reactions attributed to aromatase inhibitors as a group, mainly acne, musculoskeletal, mood and reproductive disorders, and 26% of aromatase inhibitor posts described impaired quality of life. Product identity is a separate concern: 34.9% of 63 seized post-cycle therapy products did not contain the declared active ingredient.

FEMARA label, version effective 11 June 2026: indication, estrogen suppression, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. FEMARA (letrozole) film-coated oral tablets, prescribing information, label version effective 11 June 2026. Set ID 82b77d74-085f-45ac-a7dd-1f5c038bf406.

The label approves FEMARA only for postmenopausal women: adjuvant treatment of hormone receptor-positive early breast cancer, extended adjuvant treatment after 5 years of tamoxifen, and first and second-line treatment of hormone receptor-positive or unknown advanced breast cancer. The label carries no indication in men. In postmenopausal women with advanced breast cancer, daily doses of 0.1 to 5 mg suppressed plasma estradiol, estrone and estrone sulfate by 75 to 95% from baseline, with maximal suppression within 2 to 3 days, and plasma LH and FSH were not affected in those patients. Letrozole is rapidly and completely absorbed, food does not affect absorption, the terminal elimination half-life is about 2 days, and steady state is reached in 2 to 6 weeks of daily dosing. In BIG 1-98 (NCT00004205, over 8,000 women), the monotherapy-arms analysis at a median 73 months found disease-free survival favored letrozole over tamoxifen (HR 0.87, 95% CI 0.76 to 0.99, P = 0.03; 445 versus 500 events among 2,463 and 2,459 women). Warnings cover lower bone mineral density (median lumbar spine change of -4.1% with letrozole versus +0.3% with tamoxifen at 24 months in a 263-woman safety study), fractures (14.7% versus 11.4% with tamoxifen in BIG 1-98 at median 96 months), hypercholesterolemia (52.3% versus 28.6%), fatigue, dizziness, somnolence and embryo-fetal toxicity. Safety and effectiveness in pediatric patients have not been established, and, based on studies in male animals, FEMARA may impair fertility in males of reproductive potential.

Participants / model
Postmenopausal women with breast cancer; label PK participants
Treatment
FEMARA 2.5 mg film-coated oral tablets
Follow-up
Label version effective 11 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The estrogen-suppression figures come from postmenopausal women and should not be transferred to men. The label carries no indication in men.

Read the original source
296 infertile men, 3 months: sperm category upgrade 14.3% versus 5.4%, decreased libido 12.2% versus 5.4%

Randomized controlled trial

Sun Y et al. JAMA Netw Open. 2026;9(6):e2618422. PMID 42313386.

The WHO sperm concentration category upgrade rate was 14.3% (21 of 147) versus 5.4% (8 of 149) (risk difference 9.2%, 95% CI 2.5 to 15.8%, P = 0.01), with no significant between-group difference in semen parameters. Letrozole raised gonadotropins and testosterone and lowered estradiol. Decreased libido was reported by 18 men (12.2%) on letrozole versus 8 (5.4%) on control (P = 0.04).

Participants / model
296 men with spermatogenic failure (73.6% with nonobstructive azoospermia), mean age 30.2 years
Treatment
Oral letrozole 2.5 mg daily plus vitamins C and E, or vitamins alone
Follow-up
3 months
Study design
2026 multicenter randomized trial, open-label with assessor blinding
Funding
not stated in the source

The men were infertile, not steroid users. Endpoints were the WHO sperm concentration category upgrade, semen parameters, reproductive hormones and adverse events.

Read the original source
Narrative review: aromatase inhibitors probably ineffective in gynecomastia in the young

Human study

Wit JM et al. Nat Rev Endocrinol. 2011;8(3):135-47. PMID 22024975.

The review concluded that aromatase inhibitors are probably ineffective in gynecomastia. It also found they appear effective for raising adult height in boys with short stature or pubertal delay, with safety concerns that include vertebral deformities, lower HDL cholesterol and higher erythrocytosis.

Participants / model
Children and adolescents (narrative review)
Treatment
Oral letrozole and anastrozole
Follow-up
Not applicable
Study design
Narrative review
Funding
not stated in the source

Pediatric evidence, not adult steroid users.

Read the original source
1,792 forum posts, 2013 to 2019: median letrozole course 30 days at a mean 2 mg a day

Human study

Rochoy M et al. Therapie. 2022;77(6):683-691. PMID 35660259.

Aromatase inhibitors were used mainly to fight androgen aromatization. Among five drugs analyzed, the median letrozole course was 30 days at a mean 2 mg a day, and the drugs were mainly bought online. The 62 adverse drug reactions attributed to aromatase inhibitors as a group were mainly acne, musculoskeletal, mood and reproductive disorders, and impaired quality of life was described in 26% of aromatase inhibitor posts.

Participants / model
Men posting on one anabolic steroid forum, mean age 28.2 years
Treatment
Self-sourced oral letrozole, self-reported doses
Follow-up
Posts from 2013 to 2019
Study design
Observational analysis of 1,792 forum posts
Funding
not stated in the source

This records how the drug is used, not whether it works. Doses and reactions are self-reported, and the reactions are attributed to aromatase inhibitors as a group.

Read the original source
63 seized products, 2020 to 2024: 34.9% lacked the declared ingredient

Regulatory record

Blazewicz A et al. Front Chem. 2025;13:1536858. PMID 40177353.

Poland's official medicines control laboratory tested 63 seized illegal post-cycle therapy products labeled as SERMs, aromatase inhibitors (anastrozole, letrozole, exemestane) or other agents such as hCG and cabergoline. The declared active ingredient was present in 65.1% and absent in 34.9% (reported as 20.6% with no active ingredient and 14.3% with other undeclared ingredients), and 6.4% contained an extra undeclared ingredient. Per-drug results are not given in the abstract.

Participants / model
Seized products, not a clinical population (63 of 601 samples)
Treatment
Illegal post-cycle therapy products as seized
Follow-up
Products seized 2020 to 2024
Study design
Official laboratory product analysis
Funding
not stated in the source

No letrozole-specific purity figure exists in this record. A gray-market product may not be the drug tested in the studies on this page.

Read the original source

Why does letrozole sit in A tier?

The A rests on an FDA approval since 1997 and phase 3 data for breast cancer in postmenopausal women. It does not cover the supplier's use in men, where estradiol falls but the outcomes did not follow and no study found tests letrozole for gynecomastia or estrogen control in steroid users.

The A applies to postmenopausal breast cancer. The supplier's use is a separate question. Letrozole does lower estradiol in men and raises testosterone and LH sharply, so the mechanism is partly supported. The outcomes are not: obese men with low testosterone had no somatic or psychological benefit despite testosterone rising from 8.6 to 21.5 nmol/L, and men with spermatogenic failure reported more decreased libido.

A European guideline does not recommend aromatase inhibitors for gynecomastia in general, a review of pediatric use calls them probably ineffective for gynecomastia and flags vertebral deformities, and the searches run on 10 October 2026 found no controlled trial for gynecomastia or water retention in men. The only trial in steroid users found has no abstract, so nothing is said about its results.

FEMARA label, version effective 11 June 2026: indication, estrogen suppression, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. FEMARA (letrozole) film-coated oral tablets, prescribing information, label version effective 11 June 2026. Set ID 82b77d74-085f-45ac-a7dd-1f5c038bf406.

The label approves FEMARA only for postmenopausal women: adjuvant treatment of hormone receptor-positive early breast cancer, extended adjuvant treatment after 5 years of tamoxifen, and first and second-line treatment of hormone receptor-positive or unknown advanced breast cancer. The label carries no indication in men. In postmenopausal women with advanced breast cancer, daily doses of 0.1 to 5 mg suppressed plasma estradiol, estrone and estrone sulfate by 75 to 95% from baseline, with maximal suppression within 2 to 3 days, and plasma LH and FSH were not affected in those patients. Letrozole is rapidly and completely absorbed, food does not affect absorption, the terminal elimination half-life is about 2 days, and steady state is reached in 2 to 6 weeks of daily dosing. In BIG 1-98 (NCT00004205, over 8,000 women), the monotherapy-arms analysis at a median 73 months found disease-free survival favored letrozole over tamoxifen (HR 0.87, 95% CI 0.76 to 0.99, P = 0.03; 445 versus 500 events among 2,463 and 2,459 women). Warnings cover lower bone mineral density (median lumbar spine change of -4.1% with letrozole versus +0.3% with tamoxifen at 24 months in a 263-woman safety study), fractures (14.7% versus 11.4% with tamoxifen in BIG 1-98 at median 96 months), hypercholesterolemia (52.3% versus 28.6%), fatigue, dizziness, somnolence and embryo-fetal toxicity. Safety and effectiveness in pediatric patients have not been established, and, based on studies in male animals, FEMARA may impair fertility in males of reproductive potential.

Participants / model
Postmenopausal women with breast cancer; label PK participants
Treatment
FEMARA 2.5 mg film-coated oral tablets
Follow-up
Label version effective 11 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The estrogen-suppression figures come from postmenopausal women and should not be transferred to men. The label carries no indication in men.

Read the original source
Drugs@FDA: FEMARA approved 25 July 1997

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 020726 (FEMARA). Dates read from the openFDA Drugs@FDA record.

FDA first approved FEMARA under NDA 020726 on 25 July 1997. The sponsor on the openFDA record is Novartis.

Participants / model
Not a clinical population
Treatment
Drug application
Follow-up
Approved 1997
Study design
FDA application record
Funding
not stated in the source

This record gives the approval date and sponsor. Indications come from the product label.

Read the original source
42 obese men, 6 months: testosterone up from 8.6 to 21.5 nmol/L, no somatic effect

Randomized controlled trial

Loves S et al. Eur J Endocrinol. 2013;169(5):705-14. PMID 23949882.

Estradiol fell from 119.1 to 59.2 pmol/L, LH rose from 3.3 to 8.8 U/L and total testosterone rose from 8.6 to 21.5 nmol/L, but no significant effects were seen on the predefined psychological, body composition, exercise capacity, glucose, lipid or bone endpoints. The authors concluded that a marked testosterone rise did not produce somatic or psychological effects in these men.

Participants / model
42 obese men (BMI over 35 kg/m2) with total testosterone under 10 nmol/L
Treatment
Oral letrozole dose-escalated monthly toward a testosterone target of 20 nmol/L, or placebo
Follow-up
6 months
Study design
Double-blind placebo-controlled randomized trial
Funding
not stated in the source

Obese men with low testosterone, not steroid users. Endpoints were psychological function, body composition, exercise capacity, glucose, lipids and bone metabolism.

Read the original source
296 infertile men, 3 months: sperm category upgrade 14.3% versus 5.4%, decreased libido 12.2% versus 5.4%

Randomized controlled trial

Sun Y et al. JAMA Netw Open. 2026;9(6):e2618422. PMID 42313386.

The WHO sperm concentration category upgrade rate was 14.3% (21 of 147) versus 5.4% (8 of 149) (risk difference 9.2%, 95% CI 2.5 to 15.8%, P = 0.01), with no significant between-group difference in semen parameters. Letrozole raised gonadotropins and testosterone and lowered estradiol. Decreased libido was reported by 18 men (12.2%) on letrozole versus 8 (5.4%) on control (P = 0.04).

Participants / model
296 men with spermatogenic failure (73.6% with nonobstructive azoospermia), mean age 30.2 years
Treatment
Oral letrozole 2.5 mg daily plus vitamins C and E, or vitamins alone
Follow-up
3 months
Study design
2026 multicenter randomized trial, open-label with assessor blinding
Funding
not stated in the source

The men were infertile, not steroid users. Endpoints were the WHO sperm concentration category upgrade, semen parameters, reproductive hormones and adverse events.

Read the original source
European Academy of Andrology guideline: no aromatase inhibitors for gynecomastia in general

Human study

Kanakis GA et al. Andrology. 2019;7(6):778-793. PMID 31099174.

The guideline does not recommend selective estrogen receptor modulators, aromatase inhibitors or non-aromatizable androgens for gynecomastia in general (recommendation 14, strong, low-quality evidence). It recommends watchful waiting after a substance associated with gynecomastia is stopped, and states that in more than 90% of cases pubertal gynecomastia resolves spontaneously within 24 months. The abstract does not name letrozole.

Participants / model
Boys and men with gynecomastia (guideline scope)
Treatment
Not drug-specific
Follow-up
Not applicable
Study design
Clinical practice guideline (GRADE)
Funding
not stated in the source

A recommendation for gynecomastia in general. It is not specific to letrozole.

Read the original source
PubMed searches, 10 October 2026: 8 records and 8 records, none testing the supplier claim

PubMed search record

PubMed searches run on 10 October 2026: (1) letrozole[tiab] AND (anabolic steroid*[tiab] OR anabolic-androgenic[tiab] OR anabolic androgenic[tiab] OR bodybuild*[tiab]); (2) letrozole[tiab] AND (gynecomastia[tiab] OR gynaecomastia[tiab] OR "water retention"[tiab] OR "fluid retention"[tiab]) AND (men[tiab] OR male*[tiab] OR boys[tiab]). 8 and 8 records returned.

The first search returned 8 records: a rodent neurogenesis review, three drug-detection method papers (urine and hair), a case report of rhabdomyolysis with dexmethylphenidate and an aromatase inhibitor, the forum and seized-product analyses described on this page, and the former-user trial whose abstract is not available. Apart from that trial, none tested letrozole for estrogen control, gynecomastia or water retention in men using steroids. The second search returned 8 records: three reviews, two mouse studies, a single-child Peutz-Jeghers case report, an aromatase excess syndrome family report and a urine detection paper. None was a controlled trial of letrozole for gynecomastia or water retention in men.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source

Studies and sources

FEMARA label, version effective 11 June 2026: indication, estrogen suppression, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. FEMARA (letrozole) film-coated oral tablets, prescribing information, label version effective 11 June 2026. Set ID 82b77d74-085f-45ac-a7dd-1f5c038bf406.

The label approves FEMARA only for postmenopausal women: adjuvant treatment of hormone receptor-positive early breast cancer, extended adjuvant treatment after 5 years of tamoxifen, and first and second-line treatment of hormone receptor-positive or unknown advanced breast cancer. The label carries no indication in men. In postmenopausal women with advanced breast cancer, daily doses of 0.1 to 5 mg suppressed plasma estradiol, estrone and estrone sulfate by 75 to 95% from baseline, with maximal suppression within 2 to 3 days, and plasma LH and FSH were not affected in those patients. Letrozole is rapidly and completely absorbed, food does not affect absorption, the terminal elimination half-life is about 2 days, and steady state is reached in 2 to 6 weeks of daily dosing. In BIG 1-98 (NCT00004205, over 8,000 women), the monotherapy-arms analysis at a median 73 months found disease-free survival favored letrozole over tamoxifen (HR 0.87, 95% CI 0.76 to 0.99, P = 0.03; 445 versus 500 events among 2,463 and 2,459 women). Warnings cover lower bone mineral density (median lumbar spine change of -4.1% with letrozole versus +0.3% with tamoxifen at 24 months in a 263-woman safety study), fractures (14.7% versus 11.4% with tamoxifen in BIG 1-98 at median 96 months), hypercholesterolemia (52.3% versus 28.6%), fatigue, dizziness, somnolence and embryo-fetal toxicity. Safety and effectiveness in pediatric patients have not been established, and, based on studies in male animals, FEMARA may impair fertility in males of reproductive potential.

Participants / model
Postmenopausal women with breast cancer; label PK participants
Treatment
FEMARA 2.5 mg film-coated oral tablets
Follow-up
Label version effective 11 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The estrogen-suppression figures come from postmenopausal women and should not be transferred to men. The label carries no indication in men.

Read the original source
Drugs@FDA: FEMARA approved 25 July 1997

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 020726 (FEMARA). Dates read from the openFDA Drugs@FDA record.

FDA first approved FEMARA under NDA 020726 on 25 July 1997. The sponsor on the openFDA record is Novartis.

Participants / model
Not a clinical population
Treatment
Drug application
Follow-up
Approved 1997
Study design
FDA application record
Funding
not stated in the source

This record gives the approval date and sponsor. Indications come from the product label.

Read the original source
20 healthy men, 28 days: estradiol down, LH and testosterone up

Human study

T'Sjoen GG et al. J Clin Endocrinol Metab. 2005;90(10):5717-22. PMID 16046582.

Letrozole lowered estradiol by 46% in the young men and 62% in the elderly men, raised LH by 339% and 323%, and raised testosterone by 146% and 99%. The endpoints were free estradiol, LH, FSH, free testosterone, SHBG and GnRH response. There was no gynecomastia, body composition or symptom endpoint.

Participants / model
10 healthy young men and 10 healthy elderly men
Treatment
Oral letrozole 2.5 mg daily for 28 days, versus placebo, with a 2-week washout between
Follow-up
28 days of letrozole
Study design
Comparative intervention study: placebo, then letrozole
Funding
not stated in the source

A hormone study. It shows that letrozole lowers estradiol in healthy men and that testosterone and LH rise sharply, and it says nothing about gynecomastia or symptoms.

Read the original source
42 obese men, 6 months: testosterone up from 8.6 to 21.5 nmol/L, no somatic effect

Randomized controlled trial

Loves S et al. Eur J Endocrinol. 2013;169(5):705-14. PMID 23949882.

Estradiol fell from 119.1 to 59.2 pmol/L, LH rose from 3.3 to 8.8 U/L and total testosterone rose from 8.6 to 21.5 nmol/L, but no significant effects were seen on the predefined psychological, body composition, exercise capacity, glucose, lipid or bone endpoints. The authors concluded that a marked testosterone rise did not produce somatic or psychological effects in these men.

Participants / model
42 obese men (BMI over 35 kg/m2) with total testosterone under 10 nmol/L
Treatment
Oral letrozole dose-escalated monthly toward a testosterone target of 20 nmol/L, or placebo
Follow-up
6 months
Study design
Double-blind placebo-controlled randomized trial
Funding
not stated in the source

Obese men with low testosterone, not steroid users. Endpoints were psychological function, body composition, exercise capacity, glucose, lipids and bone metabolism.

Read the original source
296 infertile men, 3 months: sperm category upgrade 14.3% versus 5.4%, decreased libido 12.2% versus 5.4%

Randomized controlled trial

Sun Y et al. JAMA Netw Open. 2026;9(6):e2618422. PMID 42313386.

The WHO sperm concentration category upgrade rate was 14.3% (21 of 147) versus 5.4% (8 of 149) (risk difference 9.2%, 95% CI 2.5 to 15.8%, P = 0.01), with no significant between-group difference in semen parameters. Letrozole raised gonadotropins and testosterone and lowered estradiol. Decreased libido was reported by 18 men (12.2%) on letrozole versus 8 (5.4%) on control (P = 0.04).

Participants / model
296 men with spermatogenic failure (73.6% with nonobstructive azoospermia), mean age 30.2 years
Treatment
Oral letrozole 2.5 mg daily plus vitamins C and E, or vitamins alone
Follow-up
3 months
Study design
2026 multicenter randomized trial, open-label with assessor blinding
Funding
not stated in the source

The men were infertile, not steroid users. Endpoints were the WHO sperm concentration category upgrade, semen parameters, reproductive hormones and adverse events.

Read the original source
J Intern Med 2025 trial in former steroid users: no abstract on PubMed

Human study

Rasmussen JJ et al. J Intern Med. 2025;297(1):113-116. PMID 39578999.

A randomized clinical trial titled Effects of letrozole therapy in former users of anabolic steroids was published in J Intern Med in 2025 (volume 297, pages 113 to 116) by a Copenhagen group. PubMed, Europe PMC and Crossref hold no abstract for it, so its design, dose, size and results are not described here. A registered trial from the same hospital, LUCAS (NCT05205837), tested letrozole plus intramuscular hCG against placebo in men aged 18 to 50 with hypogonadism from illicit anabolic steroid use. It was terminated with 8 participants enrolled and has no posted results. Whether the two records describe the same study is not established.

Participants / model
Former anabolic steroid users (title only); the registry record lists men aged 18 to 50 with steroid-induced hypogonadism
Treatment
Oral letrozole, details not described; the registry record lists letrozole plus intramuscular hCG
Follow-up
not stated in the source
Study design
Randomized clinical trial by title; abstract not available
Funding
not stated in the source

Its title places the question in former users (post-cycle), not in men on cycle. Nothing about its results is described on this page.

Read the original source
Narrative review: aromatase inhibitors probably ineffective in gynecomastia in the young

Human study

Wit JM et al. Nat Rev Endocrinol. 2011;8(3):135-47. PMID 22024975.

The review concluded that aromatase inhibitors are probably ineffective in gynecomastia. It also found they appear effective for raising adult height in boys with short stature or pubertal delay, with safety concerns that include vertebral deformities, lower HDL cholesterol and higher erythrocytosis.

Participants / model
Children and adolescents (narrative review)
Treatment
Oral letrozole and anastrozole
Follow-up
Not applicable
Study design
Narrative review
Funding
not stated in the source

Pediatric evidence, not adult steroid users.

Read the original source
European Academy of Andrology guideline: no aromatase inhibitors for gynecomastia in general

Human study

Kanakis GA et al. Andrology. 2019;7(6):778-793. PMID 31099174.

The guideline does not recommend selective estrogen receptor modulators, aromatase inhibitors or non-aromatizable androgens for gynecomastia in general (recommendation 14, strong, low-quality evidence). It recommends watchful waiting after a substance associated with gynecomastia is stopped, and states that in more than 90% of cases pubertal gynecomastia resolves spontaneously within 24 months. The abstract does not name letrozole.

Participants / model
Boys and men with gynecomastia (guideline scope)
Treatment
Not drug-specific
Follow-up
Not applicable
Study design
Clinical practice guideline (GRADE)
Funding
not stated in the source

A recommendation for gynecomastia in general. It is not specific to letrozole.

Read the original source
1,792 forum posts, 2013 to 2019: median letrozole course 30 days at a mean 2 mg a day

Human study

Rochoy M et al. Therapie. 2022;77(6):683-691. PMID 35660259.

Aromatase inhibitors were used mainly to fight androgen aromatization. Among five drugs analyzed, the median letrozole course was 30 days at a mean 2 mg a day, and the drugs were mainly bought online. The 62 adverse drug reactions attributed to aromatase inhibitors as a group were mainly acne, musculoskeletal, mood and reproductive disorders, and impaired quality of life was described in 26% of aromatase inhibitor posts.

Participants / model
Men posting on one anabolic steroid forum, mean age 28.2 years
Treatment
Self-sourced oral letrozole, self-reported doses
Follow-up
Posts from 2013 to 2019
Study design
Observational analysis of 1,792 forum posts
Funding
not stated in the source

This records how the drug is used, not whether it works. Doses and reactions are self-reported, and the reactions are attributed to aromatase inhibitors as a group.

Read the original source
63 seized products, 2020 to 2024: 34.9% lacked the declared ingredient

Regulatory record

Blazewicz A et al. Front Chem. 2025;13:1536858. PMID 40177353.

Poland's official medicines control laboratory tested 63 seized illegal post-cycle therapy products labeled as SERMs, aromatase inhibitors (anastrozole, letrozole, exemestane) or other agents such as hCG and cabergoline. The declared active ingredient was present in 65.1% and absent in 34.9% (reported as 20.6% with no active ingredient and 14.3% with other undeclared ingredients), and 6.4% contained an extra undeclared ingredient. Per-drug results are not given in the abstract.

Participants / model
Seized products, not a clinical population (63 of 601 samples)
Treatment
Illegal post-cycle therapy products as seized
Follow-up
Products seized 2020 to 2024
Study design
Official laboratory product analysis
Funding
not stated in the source

No letrozole-specific purity figure exists in this record. A gray-market product may not be the drug tested in the studies on this page.

Read the original source
PubChem: letrozole identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 3902 (letrozole).

Letrozole: PubChem CID 3902, C17H11N5, 285.30 g/mol, CAS 112809-51-5. FEMARA and the generics contain letrozole itself, not a salt.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

Why is Letrozole in A tier?

A fits an approved drug promoted for an off-label use and population. Letrozole has been FDA-approved since 1997 for postmenopausal breast cancer, with phase 3 data behind it, and nothing on the label covers men. It lowers estradiol in men, but obese men with low testosterone had no somatic or psychological benefit, a European guideline advises against aromatase inhibitors for gynecomastia in general, and no study found tests it for estrogen control in men using steroids.