Some science behind the scenes

SERMs

Selective estrogen receptor modulators (SERMs) are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER 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.

SERMs are competitive partial agonists of the ER. Different tissues have different degrees of sensitivity to and activity of endogenous estrogens, so SERMs produce estrogenic or antiestrogenic effects depending on the specific tissue in question as well as the percentage of intrinsic activity (IA) of the SERM.

An example of a SERM with high IA and thus mostly estrogenic effects is chlorotrianisene, while an example of a SERM with low IA and thus mostly antiestrogenic effects is ethamoxytriphetol. SERMs like clomifene and tamoxifen are more in the middle in their IA and their balance of estrogenic and antiestrogenic actions in comparison. Raloxifene is a SERM that is more antiestrogenic than tamoxifen; both are estrogenic in bone, but raloxifene is antiestrogenic in the uterus while tamoxifen is estrogenic in this location.

SERMs are used for various estrogen-related diseases. Including

- treatment of ovulatory dysfunction in the management of infertility,
- treatment and prevention of postmenopausal osteoporosis,
 - treatment and reduction in risk [sic]  of breast cancer and
- treatment of dyspareunia due to menopause.

SERM is also used in combination with conjugated estrogens indicated for the treatment of

 - estrogen deficiency symptoms, and
- vasomotor symptoms associated with menopause.

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




Some SERMs have been known to induce hallucinations and psychosis.

Pharmaceutical companies state that these drugs are targeted because they only act specific sites.  Many researchers, however, have pointed out that the body is an integrated system and it is impossible unless one understands the entire process and its systematic effects to say this.  In fact the very conclusion that something acts on only one receptor might be entirely incorrect once one takes the full cycle of action into account.  This is born out by the research papers, for example

Menopause. 2010 May-Jun;17(3):642-53. doi: 10.1097/gme.0b013e3181c4f1d6.
Endometrial safety: a key hurdle for selective estrogen receptor modulators in development.
Pinkerton JV1, Goldstein SR.

Selective estrogen receptor modulators (SERMs) have the ability to provide mixed functional estrogen receptor (ER) agonist or antagonist activity, depending on the target tissue.

Tamoxifen, the first SERM available for clinical use, is [used] for the prevention and treatment of breast cancer. However, tamoxifen exhibits ER agonist activity in the uterus and is associated with an increased risk of endometrial hyperplasia and malignancy.

......Of the newer SERMs in development, lasofoxifene has been shown to reduce fracture risk and decrease the incidence of breast cancer but has been associated with an increased incidence of vaginal bleeding, endometrial thickening, and endometrial polyps.
.... PMID:  20107426

see the observations below.

References

  • Psychosomatics. 2007 Jan-Feb;48(1):65-6.  Manic delirium associated with clomiphene-induced ovulation.  Parikh AR1, Liskow BI.   PMID: 17209152
  • Isr J Med Sci. 1987 Nov;23(11):1156-7.  Psychotic episode induced by ovulation-initiating treatment.  Altmark D1, Tomer R, Sigal M.   PMID: 3436800
  • Am J Psychiatry. 1997 Aug;154(8):1169-70.  Clomiphene-induced psychosis.  Oyffe I, Lerner A, Isaacs G, Harel Y, Sigal M.  PMID:  9247412

Observations

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