An antiestrogen is a drug which decreases estrogen signaling in the body. They do this either by acting as antagonists of the estrogen receptor (ER) or by inhibiting or suppressing estrogen production. Examples include selective estrogen receptor modulators (SERMs) like tamoxifen and raloxifene, which are partial agonists of the ER and have mixed estrogenic and antiestrogenic effects in different tissues (but are predominantly antiestrogenic), ER antagonists like fulvestrant, which are pure or silent antagonists with no capacity to activate the estrogen receptor and hence only antiestrogenic activity, aromatase inhibitors (AIs) like anastrozole and exemestane, which inhibit aromatase or other steroidogenic enzymes and thereby prevent the production of estrogens, and antigonadotropins like GnRH analogues, high-dose progestogens, high-dose androgens/anabolic steroids, and prolactin releasers, which suppress the function of the gonads and thereby prevent them from producing estrogens as well as other sex hormones.
Antiestrogens are often used in the treatment of breast cancer in women and in the treatment of gynecomastia and hypogonadism in men. In transgender men, antiestrogens can be used as a component of hormone therapy to circumvent the effects of estrogens. In transfeminine people or androgynes who wish to become physically feminine or androgynous but do not wish to develop breasts, antiestrogens can be used in conjunction with antiandrogens to prevent breast development.
GnRH blockers lower estrogens in those with ovaries. Danazol both inhibits production of GnRH and is an antiestrogen that blocks FSH and LH in those with ovaries. Danazol also has mild androgenic effects and possibly binds to androgen receptors and progesterone receptors.
Aromatase inhibitors are used as a last resort (or with conjunction with SERMs) in the treatment of some estrogen dependent disorders. Selective aromatase inhibitors only lower estrogen levels and not those of any other steroid produced by the adrenal gland.
Some SERMs are used in the treatment of gynecomastia, as the majority of them prevent estrogen from being used in the breasts.
Letrozole (an estrogen inhibitor) has been shown to prevent growth plate fusion, so doctors sometimes use it in conjunction with growth hormone to help short children and teens gain height. It elevates LH but does not increase FSH.
Anastrozole has been used for effective gynecomastia treatment, however, exactly how it does this is unknown.
Clomifene acts as both an estrogen and an anti estrogen. Its exact mechanism of action is unknown, but it stimulates GnRH production and LH and FSH production.
List of medications
- SERMs: Include compounds like Raloxifene, Tamoxifen, Afimoxifene, and Clomifene
- Aromatase inhibitors (selective): Anastrozole, Letrozole, Exemestane
- Estrogen receptor inhibitors: Fulvestrant. Fulvestrant downregulates and degrades estrogen receptors.
- GnRH inhibitor and androgen: Danazol
- DrugBank. Clomifene. https://www.drugbank.ca/drugs/DB00882
- DrugBank. Estrogen Antagonists. https://www.drugbank.ca/categories/DBCAT000786
- Osborne CK, Wakeling A, Nicholson RI. Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action. British Journal of Cancer. 2004;90(Suppl 1):S2-S6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750773/ https://doi.org/10.1038/sj.bjc.6601629
- DrugBank. Anti-Estrogens. https://www.drugbank.ca/categories/DBCAT002405