II. Indications

  1. Postmenopausal Breast Cancer (adjuvant treatment if Estrogen or Progesterone positive)
  2. Severe Endometriosis (off-label)

III. Contraindications

  1. Pregnancy
  2. Premenopausal women

IV. Mechanism

  1. Aromatase
    1. Converts Cholesterol to pregnenolone
    2. Aromatizes peripheral androgens (Androstenedione, Testosterone) into Estrogens (estrone, Estradiol)
    3. Aromatase is a Cytochrome P-450 enzyme found on the endoplasmic reticulum of the cell
      1. Cells containing aromatase include those in the Breast, ovary and liver
  2. Aromatase Inhibitors
    1. Non-steroidal inhibitors selectively decrease circulating Estradiol levels

V. Medications

  1. Letrozole (Femara)
    1. Selective, reversible, third generation Aromatase Inhibitor
    2. More potent than Anastrozole
    3. Dosed 2.5 mg orally daily
      1. Decrease to 2.5 mg every other day in Cirrhosis or severe liver Impairment
  2. Anastrozole (Arimidex)
    1. Selective, reversible, third generation Aromatase Inhibitor
    2. Similar structure to Paclitaxel
    3. Dosed 1 mg orally daily
  3. Exemestane (Aromasin)
    1. Steroidal, synthetic androgen analog, and an irreversible Aromatase Inhibitor
    2. Dosed 25 mg orally daily
      1. Increase dose to 50 mg if concurrent use of a Strong CYP3A4 inducer
  4. Aminoglutethimide (Cytadren)
    1. Listed for historical purposes, but replaced by other Aromatase Inhibitors
    2. Synthetic derivative of glutethimide (Sedative, anticonvulsant)
    3. Blocks adrenal steroidogenesis (Cholesterol to delta5-pregnenolone)
    4. Does not decrease ovarian Estrogen production
    5. Has also been used in treating Cushing's Disease and ACTH Secreting tumors

VI. Adverse Effects

  1. Osteoporosis
    1. Decreases Bone Mineral Density, and increases risks of fragility Fractures
  2. Cardiovascular Disease Risk may be increased (including CVA risk)
    1. Hyperlipidemia
    2. Hypertension
  3. Menopausal symptoms
    1. Hot Flashes
    2. Vaginal Dryness
  4. Other common adverse effects
    1. Ovarian Follicular Cysts
    2. Gastrointestinal symptoms
    3. Headaches
    4. Arthralgias and bone pain
    5. Myalgias

VII. Safety

  1. Pregnancy Category X
  2. Unknown safety in Lactation
  3. Monitoring
    1. Bone Mineral Density (e.g. DEXA Scan)
    2. 25-hydroxy Vitamin D Level baseline

VIII. Efficacy

  1. Letrozole, Anastrazole, Exemastane appear to have similar efficacy in the adjuvant treatment of Breast Cancer
  2. More effective than Tamoxifen in reducing recurrence rates

IX. Drug Interactions

  1. Tamoxifen
    1. Avoid in combination (no significant added benefit of Tamoxifen when added to Aromatase Inhibitors)
  2. Estrogens
    1. May decrease the activity of Aromatase Inhibitors
  3. Strong CYP3A4 inducers
    1. Decreases Exemestane levels (increase dose to 50 mg daily)

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

letrozole (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
LETROZOLE 2.5 MG TABLET Generic $0.11 each
anastrozole (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ANASTROZOLE 1 MG TABLET Generic $0.11 each
exemestane (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
EXEMESTANE 25 MG TABLET Generic $0.71 each

Ontology: Aminoglutethimide (C0002555)

Definition (MSH) An aromatase inhibitor that is used in the treatment of advanced BREAST CANCER.
Definition (NCI) A synthetic derivative of the sedative and anticonvulsant glutethimide with anti-steroid properties. Originally used as an anticonvulsant, aminoglutethimide also blocks adrenal steroidogenesis by inhibiting the enzymatic conversion of cholesterol to pregnenolone. In addition, this agent blocks the peripheral aromatization of androgenic precursors to estrogens. Aminoglutethimide does not suppress ovarian estrogen production.
Definition (NCI_NCI-GLOSS) An anticancer drug that belongs to the family of drugs called nonsteroidal aromatase inhibitors. Aminoglutethimide is used to decrease the production of sex hormones (estrogen in women or testosterone in men) and suppress the growth of tumors that need sex hormones to grow.
Definition (CSP) USP lists as an antineoplastic and an "adrenocortical suppressant."
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D000616
SnomedCT 391757005, 255629008, 387257000, 47124006
English Aminoglutethimide, aminoglutethimide, 2,6-Piperidinedione, 3-(4-aminophenyl)-3-ethyl-, 2-(p-Aminophenyl)-2-ethylglutarimide, 3-Ethyl-3-(p-aminophenyl)-2,6-dioxopiperidine, 3-(4-Aminophenyl)-3-ethyl-2,6-piperidinedione, alpha-(4-Aminophenyl)-alpha-ethylglutarimide, aminoglutethimide (medication), hormones aminoglutethimide, Aminoglutethimide [Chemical/Ingredient], ag, Aminoglutethimide - chemical (substance), Aminoglutethimide - chemical, Aminoglutethimide (product), Aminoglutethimide (substance), AG, AGT, AMINOGLUTETHIMIDE
Swedish Aminoglutetimid
Czech aminoglutethimid
Finnish Aminoglutetimidi
Russian AMINOGLUTETIMID, ELIPTEN, АМИНОГЛУТЕТИМИД, ЭЛИПТЕН
Japanese アミノグルテチミド
Polish Aminoglutetymid
Spanish aminoglutetimida (producto), aminoglutetimida (sustancia), aminoglutetimida, Aminoglutetimida
French Aminoglutéthimide
German Aminoglutethimid
Italian Aminoglutetimmide
Portuguese Aminoglutetimida

Ontology: letrozole (C0246421)

Definition (NCI) A nonsteroidal inhibitor of estrogen synthesis with antineoplastic activity. As a third-generation aromatase inhibitor, letrozole selectively and reversibly inhibits aromatase, which may result in growth inhibition of estrogen-dependent breast cancer cells. Aromatase, a cytochrome P-450 enzyme localized to the endoplasmic reticulum of the cell and found in many tissues including those of the premenopausal ovary, liver, and breast, catalyzes the aromatization of androstenedione and testosterone into estrone and estradiol, the final step in estrogen biosynthesis.
Definition (NCI_NCI-GLOSS) A drug used to treat advanced breast cancer in postmenopausal women. Letrozole causes a decrease in the amount of estrogen made by the body. It is a type of aromatase inhibitor.
Definition (PDQ) A nonsteroidal inhibitor of estrogen synthesis that resembles paclitaxel in chemical structure. As a third-generation aromatase inhibitor, letrozole selectively and reversibly inhibits aromatase, a cytochrome P-450 enzyme complex found in many tissues including those of the premenopausal ovary, liver, and breast; aromatase catalyzes the aromatization of androstenedione and testosterone into estrone and estradiol, the final step in estrogen biosynthesis. In estrogen-dependent breast cancers, anastrozole may inhibit tumor growth. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42086&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42086&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1527" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C067431
SnomedCT 400459004, 108777007, 386911004
English 4,4'-(1H-1,2,4-triazol-1-yl-methylene)-bis(benzonitrile), Benzonitrile, 4,4'-(1H-1,2,4-triazol-1-ylmethylene)bis-, letrozole (medication), hormones letrozole, LETROZOLE, 4,4'-(1H-1,2,4triazol-1-ylmethylene)dibenzonitrile, letrozole [Chemical/Ingredient], letrozole, lotrozole, lotrozole (product), Letrozole, Letrozole (product), Letrozole (substance), LTZ
Spanish iotrozol, iotrozol (producto), letrozol (producto), letrozol (sustancia), letrozol

Ontology: anastrozole (C0290883)

Definition (NCI_NCI-GLOSS) An anticancer drug that is used to decrease estrogen production and suppress the growth of tumors that need estrogen to grow. It is a type of nonsteroidal aromatase inhibitor.
Definition (NCI) A nonsteroidal inhibitor of estrogen synthesis that resembles paclitaxel in chemical structure. As a third-generation aromatase inhibitor, anastrozole selectively binds to and reversibly inhibits aromatase, a cytochrome P-450 enzyme complex found in many tissues including those of the premenopausal ovary, liver, and breast; aromatase catalyzes the aromatization of androstenedione and testosterone into estrone and estradiol, the final step in estrogen biosynthesis. In estrogen-dependent breast cancers, ananstrozole may inhibit tumor growth. (NCI04)
Definition (PDQ) A nonsteroidal inhibitor of estrogen synthesis that resembles paclitaxel in chemical structure. As a third-generation aromatase inhibitor, anastrozole selectively binds to and reversibly inhibits aromatase, a cytochrome P-450 enzyme complex found in many tissues including those of the premenopausal ovary, liver, and breast; aromatase catalyzes the aromatization of androstenedione and testosterone into estrone and estradiol, the final step in estrogen biosynthesis. In estrogen-dependent breast cancers, anastrozole may inhibit tumor growth. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42540&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42540&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1607" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C090450
SnomedCT 391778008, 108774000, 386910003
English 1,3-Benzenediacetonitrile, alpha,alpha,alpha',alpha'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-, 2,2'-(5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene)bis(2-methylpropionitrile), 2,2'-[5-(1H-1,2,4-Triazol-1-ylmethyl)-1,3-phenylene]di(2-methylpropionitrile), Alpha,alpha,alpha', alpha'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-benzenediacetonitrile, hormones anastrozole, anastrozole (medication), ANASTROZOLE, anastrozole [Chemical/Ingredient], anastrazole, Anastrozole - chemical (substance), Anastrozole - chemical, Anastrozole, Anastrozole (product), Anastrozole (substance), ANAS, anastrozole
Spanish anastrozol (producto), anastrozol (sustancia), anastrozol

Ontology: Aromatase Inhibitors (C0593802)

Definition (NCI) Any substance that inhibits aromatase, an enzyme responsible for the conversion of cholesterol to pregnenolone and the peripheral aromatization of androgenic precursors into estrogens. Inhibition of aromatase results in the suppression of estrogen-regulated processes.
Definition (NCI_NCI-GLOSS) A drug that prevents the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors are used as a type of hormone therapy for postmenopausal women who have hormone-dependent breast cancer.
Definition (MSH) Compounds that inhibit AROMATASE in order to reduce production of estrogenic steroid hormones.
Definition (CSP) compound that inhibits aromatase and reduces production of estrogenic steroid hormones.
Concepts Pharmacologic Substance (T121)
MSH D047072
SnomedCT 108775004, 413575009
French Antiaromatases, Anti-aromatases, Inhibiteurs de l'aromatase
Swedish Aromatashämmare
Czech aromatasa - inhibitory
Finnish Aromataasinestäjät
Russian AROMATAZY INGIBITORY, АРОМАТАЗЫ ИНГИБИТОРЫ
English Aromatase Inhibitors, aromatase inhibitors, Aromatase inhibitors, aromatase inhibitor, Aromatase inhibitor, Aromatase inhibitor (product), Inhibitors, Aromatase, Estrogen Synthase Inhibitor, Estrogen Synthetase Inhibitor, Androstenedione Aromatase Inhibitor, Aromatase Inhibitor, Aromatase inhibitor (substance)
Polish Inhibitory aromatazy
Portuguese Inibidores de Aromatase, Inibidores da Aromatase
Spanish inhibidor de aromatasa (producto), inhibidor de aromatasa, inhibidor de aromatasa (sustancia), Inhibidores de la Aromatasa
German Aromatase-Inhibitoren
Italian Inibitori dell'aromatasi

Ontology: exemestane (C0851344)

Definition (NCI_NCI-GLOSS) A drug used to treat advanced breast cancer and to prevent recurrent breast cancer in postmenopausal women who have already been treated with tamoxifen. It is also being studied in the treatment of other types of cancer. Aromasin causes a decrease in the amount of estrogen made by the body. It is a type of aromatase inhibitor.
Definition (NCI) A synthetic androgen analogue. Exemestane binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the conversion of cholesterol to pregnenolone and the peripheral aromatization of androgenic precursors into estrogens. (NCI04)
Definition (PDQ) A synthetic androgen analogue. Exemestane binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the conversion of cholesterol to pregnenolone and the peripheral aromatization of androgenic precursors into estrogens. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42297&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42297&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1097" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Steroid (T110)
MSH C056516
SnomedCT 327382008, 116115004, 387017005
English 6-methyleneandrosta-1,4-diene-3,17-dione, exemestane, 6-Methyleneandrosta-1,4-diene-3,17-dione, exemestane (medication), EXEMESTANE, exemestane [Chemical/Ingredient], Exemestane (product), Exemestane (substance), Exemestane
Spanish exemestano (producto), exemestano (sustancia), exemestano