Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

s which prevent

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

s like

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

from mediating their biological effects in the body. They act by blocking the

estrogen receptor Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

(ER) and/or inhibiting or suppressing estrogen production., Antiestrogens are one of three types of sex hormone antagonists, the others being

antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking t ...

s and antiprogestogens. Antiestrogens are commonly used to stop steroid hormones, estrogen, from binding to the estrogen receptors leading to the decrease of estrogen levels. Decreased levels of estrogen can lead to complications in sexual development.

Types and examples

Antiestrogens include

selective estrogen receptor modulator Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonists/antagonists (ERAAs), are a class of drugs that act on estrogen receptors (ERs). Compared to pure ER agonists–antagonists (e.g., full agonists and silent ...

s (SERMs) like

tamoxifen Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and men. It is also being studied for other types of cancer. It has been used for Albright syndrome ...

clomifene Clomifene, also known as clomiphene, is a medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome. It is taken by mouth. Common side effects include pelvic pain and hot flashes. Oth ...

, and raloxifene, the ER

silent antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...

and selective estrogen receptor degrader (SERD) fulvestrant,

aromatase inhibitor Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and in men, and gynecomastia in men. They may also be used off-label to reduce estrogen conversion when supplementing testosterone exo ...

s (AIs) like

anastrozole Anastrozole, sold under the brand name Arimidex among others, is an antiestrogenic medication used in addition to other treatments for breast cancer. Specifically it is used for hormone receptor-positive breast cancer. It has also been used t ...

, and

antigonadotropin An antigonadotropin is a drug which suppresses the activity and/or downstream effects of one or both of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This results in an inhibition of the hypothalamic-pituit ...

s including

androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

anabolic steroid Anabolic steroids, also known as anabolic-androgenic steroids (AAS), are a class of drugs that are structurally related to testosterone, the main male sex hormone, and produce effects by binding to the androgen receptor (AR). Anabolism, Anaboli ...

progestogen Progestogens, also sometimes written progestins, progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestoge ...

s, and GnRH analogues. Estrogen receptors (ER) like ERα and ERβ include activation function 1 (AF1) domain and activation function 2 (AF2) domain in which SERMS act as antagonists for the AF2 domain, while “pure” antiestrogens like ICI 182,780 and ICI 164,384 are antagonists for the AF1 and AF2 domains. Although

s and antigonadotropins can be considered antiestrogens by some definitions, they are often treated as distinct classes. Aromatase inhibitors and antigonadotropins reduce the ''production'' of estrogen, while the term "antiestrogen" is often reserved for agents reducing the ''response'' to estrogen.

Medical uses

Antiestrogens are used for: * Estrogen deprivation therapy in the treatment of ER-positive

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

Ovulation induction Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles to reverse anovulation or oligoovulation. Scope The term ''ovulation induction'' can p ...

infertility In biology, infertility is the inability of a male and female organism to Sexual reproduction, reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, whi ...

due to

anovulation Anovulation is when the ovaries do not release an oocyte during a menstrual cycle. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause. Chronic anovulat ...

Male hypogonadism Hypogonadism means diminished functional activity of the gonads—the testicles or the ovaries—that may result in diminished production of sex hormones. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low est ...

Gynecomastia Gynecomastia (also spelled gynaecomastia) is the non-cancerous enlargement of one or both breasts in men due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (10 Novemb ...

(

breast development Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a female's life. It occurs across several phases, including prenatal development, puberty, and pregnancy. At menopause, breas ...

in men) * A component of

hormone replacement therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such ...

for

transgender men A trans man or transgender man is a man who was assigned female at birth. Trans men have a male gender identity, and many trans men undergo medical and social transition to alter their appearance in a way that aligns with their gender identi ...

Side effects

women A woman is an adult female human. Before adulthood, a female child or adolescent is referred to as a girl. Typically, women are of the female sex and inherit a pair of X chromosomes, one from each parent, and women with functional u ...

, the

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of antiestrogens include

hot flash Hot flushes are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and may typically last from t ...

es,

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...

, breast atrophy,

vaginal dryness Vaginal lubrication is a naturally produced fluid that lubricates the vagina. Vaginal lubrication production increases significantly during sexual arousal in anticipation of sexual intercourse. Vaginal dryness is the condition in which this l ...

, and vaginal atrophy. In addition, they may cause depression and reduced

libido In psychology, libido (; ) is psychic drive or energy, usually conceived of as sexual in nature, but sometimes conceived of as including other forms of desire. The term ''libido'' was originally developed by Sigmund Freud, the pioneering origin ...

Pharmacology

Antiestrogens act as

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.estrogen receptor Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

ERα Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the se ...

and

ERβ Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by t ...

History

The first nonsteroidal antiestrogen was discovered by Lerner and coworkers in 1958. Ethamoxytriphetol (MER-25) was the first antagonist of the ER to be discovered, followed by

and

References

External links

* {{Estrogen receptor modulators Hormonal antineoplastic drugs Progonadotropins