Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of
drugs which prevent
estrogens like
estradiol from mediating their
biological effect
In evolutionary biology, function is the reason some object or process occurred in a system that evolved through natural selection. That reason is typically that it achieves some result, such as that chlorophyll helps to capture the energy of sunl ...
s in the body. They act by
blocking the
estrogen receptor (ER) and/or
inhibiting or
suppressing estrogen
production.
[,] Antiestrogens are one of three types of
sex hormone antagonists, the others being
antiandrogens 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. Antiandrogens are sex hormone antagonists which are able to lower the production and the effects that testosterone can have on female bodies.
Types and examples
Antiestrogens include
selective estrogen receptor modulators (SERMs) like
tamoxifen,
clomifene, and
raloxifene, the ER
silent antagonist and
selective estrogen receptor degrader (SERD)
fulvestrant,
s (AIs) like
anastrozole, and
antigonadotropins including
androgens/
anabolic steroids,
progestogens, 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
aromatase inhibitors 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
Estrogen deprivation therapy, also known as endocrine therapy, is a form of hormone therapy that is used in the treatment of breast cancer. Modalities include antiestrogens or estrogen blockers such as selective estrogen receptor modulators (SERMs) ...
in the treatment of ER-positive
breast cancer
*
Ovulation induction in
infertility due to
anovulation
*
Male hypogonadism
Hypogonadism means diminished functional activity of the gonads—the testes 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 estrogen ...
*
Gynecomastia (
breast development in men)
* A component of
hormone replacement therapy for
transgender men
A trans man is a man who was assigned female at birth. The label of transgender man is not always interchangeable with that of transsexual man, although the two labels are often used in this way. ''Transgender'' is an umbrella term that incl ...
Side effects
Side effects of antiestrogens include
hot flash
Hot flashes (also known as 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, an ...
es,
osteoporosis,
breast atrophy
Breast atrophy is the normal or spontaneous atrophy or shrinkage of the breasts.
Breast atrophy commonly occurs in women during menopause when estrogen levels decrease. It can also be caused by hypoestrogenism and/or hyperandrogenism in women in ...
,
vaginal dryness
Vaginal lubrication is a naturally produced fluid that lubricates a
vagina. Vaginal lubrication is always present, but production increases significantly near ovulation and during sexual arousal in anticipation of sexual intercourse. Vaginal dr ...
, and
vaginal atrophy. In addition, they may cause
depression and reduced
libido.
Pharmacology
Antiestrogens act as
antagonists of the
estrogen receptors,
ERα and
ERβ.
History
The first nonsteroidal antiestrogen was discovered by Lerner and coworkers in 1958.
(MER-25) was the first antagonist of the ER to be discovered,
followed by
clomifene and
tamoxifen.
See also
*
Antiestrogen withdrawal response
*
Estrogen synthesis inhibitor
References
External links
*
{{Estrogen receptor modulators
Hormonal antineoplastic drugs
Progonadotropins