Selective estrogen receptor modulator

These bottles and pills are of the drugs tamoxifen and raloxifene that are being used in a breast cancer prevention trial (STAR).

Selective Estrogen Receptor Modulators (SERMs) are a class of compounds that act on the estrogen receptor.^[1] A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues. Phytoserms are scientifically accepted SERMs from a botanical source.

Members

Members include:

• afimoxifene (4-hydroxytamoxifen)
• arzoxifene
• bazedoxifene
• clomifene
• femarelle (DT56a)^[2]
• lasofoxifene
• ormeloxifene
• raloxifene
• tamoxifen
• toremifene

Uses

SERMs are used dependent on their pattern of action in various tissues:

• clomifene is used in anovulation
• femarelle is used for managing menopause symptoms and maintaining bone health
• ormeloxifene is used for contraception
• raloxifene is used for osteoporosis and reducing risk of invasive breast cancer
• tamoxifen and toremifene are used for breast cancer

Some SERMs may be good replacements for hormone replacement therapy (HRT), which had been commonly used to treat menopause symptoms until the publication of wide scale studies showing that HRT slightly increases the risk of breast cancer ^[3] and thrombosis.^[4] Some of the above agents still have significant side-effects which contraindicate widespread use.

SERMs are also commonly used during PCT or Post Cycle Therapy after the use of anabolic steroids, or during a steroid cycle in case of the sudden onset of estrogenic symptoms. Bodybuilders who take hormonal supplements can experience gynecomastia and similar symptoms because the body metabolizes some steroids into estrogen. This increase in estrogen can occur during or after a steroid cycle, so responsible body builders will usually cycle a SERM after a steroid cycle to ensure that their body is not flooded with excess estrogen. They also often keep a SERM on hand in case of emergency.

Mechanism of action

Estrogenic compounds span a spectrum of activity ranging from:

• full agonists (agonistic in all tissues) such as the natural endogenous hormone estrogen
• mixed agonists/antagonistics (agonistic in some tissues while antagonist in others) such as tamoxifen (a SERM)
• pure antagonists (antagonistic in all tissues) such as fulvestrant (ICI-182780).

The mechanism of mixed agonism/antagonism may differ depending on the chemical structure of the SERM, but for at least for some SERMs, it appears to be related to (1) the ratio of co-activator to co-repressor proteins in different cell types and (2) the conformation of the estrogen receptor induced by drug binding which in turn determines how strongly the drug/receptor complex recruits co-activators (resulting in an agonist response) relative to co-repressors (resulting in antagonism). For example, the prototypical SERM tamoxifen acts as an antagonist in breast and conversely an agonist in uterus. The concentration of steroid receptor co-activator 1 (SRC-1; NCOA1) is higher in uterus than in breast, therefore SERMs such as tamoxifen are more agonistic in uterus than in breast. In contrast, raloxifene behaves as an antagonist in both tissues. It appears that raloxifene more strongly recruits co-repressor proteins and consequently is still an antagonist in the uterus despite the higher concentration of co-activators relative to co-repressors.^[5][6]

Actions

The actions of SERMs on various tissues:

• Bone turnover and postmenopausal osteoporosis respond favorably to most SERMs.
• Breast - all SERMs decrease breast cancer risk, and tamoxifen is mainly used for its ability to inhibit growth in estrogen receptor-positive breast cancer.
• Cholesterol and triglycerides - levels respond favorably to SERMs.
• Deep venous thrombosis - the risk may be elevated in at least some SERMs.
• Hot flashes are increased by some SERMs.
• Pituitary gland - clomifene blocks estrogen action, leading to an increase of follicle-stimulating hormone.
• Uterus - tamoxifen may increase endometrial carcinoma risk, but raloxifene and femarelle do not. Data on toremifene and clomifene is insufficient.

References

See also

• Selective receptor modulator
• Selective androgen receptor modulator
• Selective progesterone receptor modulator
• Selective glucocorticoid receptor agonist
• Phytoserm
• Femarelle
• Lasofoxifene
• Ormeloxifene
• Raloxifene
• Tamoxifen
• Toremifene

External links

• AACR Cancer Concepts Factsheet on SERMs
• STAR: a head-to-head comparison of tamoxifen and raloxifene as breast-cancer preventatives
• Femarelle official site
• Raloxifene (Evista) official site