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Selective estrogen receptor modulators (SERM)

Aug. 7, 2019

Selective estrogen receptor modulators (SERMs) are chemical compounds, which resemble estrogens, but which are not steroids. Nevertheless, they can bind to estrogen receptors [1].

Depending on the target tissue, SERMs can act as either estrogen agonists or estrogen antagonists. They can act like estrogen in one tissue and like an anti-estrogen in another tissue [2]. For example, SERMs can induce estrogenic effects on the skeletal and circulatory systems but inhibit these effects on the breasts and the uterus [3]. Therefore, SERMS differ from estrogens that can act as agonists only, and from anti-estrogens that act as antagonists only [1].

Chemically speaking, SERMs can be divided into five groups as follows: triphenylethylenes (for instance, tamoxifen and clomiphene), benzothiophenes, tetrahydronaphthalenes, indoles, and benzopyrans [3]. Tamoxifen and clomiphene are classified as doping substances pursuant to a decree issued by the Finnish Government, [4].
 

Medical uses and mechanism of action

The management of female menopause with estrogen often induces numerous adverse effects so that these may override the benefits. SERMs are thought to provide most of the estrogen benefits with less harm [1]. In addition to female menopause management, SERMs are used in treatments for breast cancer, osteoporosis, and male infertility.

Clomiphene is used in the treatment of ovarian infertility, but to stimulate testicular activity in men as well [3]. Clomiphene inhibits the negative feedback loop of the hypothalamus and the pituitary gland in men. This leads to the increased secretion of the luteinizing hormone (LH) and the follicle-stimulating hormone (FSH) in the pituitary gland. The LH and the FSH bring on increasing testosterone and sperm production. In the treatment for low testosterone, clomiphene can be of benefit when the man has a low testosterone value, but a normal testosterone/estradiol (T/E) ratio [5].

In general, tamoxifen is used for the treatment of estrogen-dependent cancers [3].
 

Purpose of use as a doping substance

Testosterone and some of the anabolic androgenic steroids can metabolize into estrogen and other estrogen agonists. Men who use large quantities of anabolic androgenic steroids may have quantities of estrogen in their bloodstreams that are equivalent to the quantities found in women of reproductive age. This may lead, for instance, to the growth of breasts (gynecomastia) or other feminine features in men and low gonadotrophin and testosterone counts [6, 7, 8].

SERM users aim to prevent or reduce gynecomastia and to increase the body’s testosterone levels. Tamoxifen and clomiphene are the most typical SERMs used by men for these purposes. Clomiphene is often used after a cycle of anabolic androgenic steroid use to inhibit the negative feedback of estrogen for the production of gonadotrophins (the LH and the FSH). Tamoxifen is used more for the self-treatment of gynecomastia than for the self-treatment of lowered testosterone values [6, 7].

Because the mechanisms of female testosterone production are different from those in men, tamoxifen and clomiphene do not induce any rise in testosterone levels in women [9].
 

Adverse effects

Some of the adverse effects of tamoxifen in men can include a weakening of the libido, impotence, hot flashes, mood swings, weight gain, and fatigue. Tamoxifen also increases the risk of phlebothrombosis [10]. It is recommended that medication with tamoxifen should involve regular checkups to determine the blood counts, serum calcium values, and liver function values [11].

Clomiphene is a safe medicine that is tolerated quite well. The most typical adverse effects include gastrointestinal upset, vertigo, hair loss, gynecomastia and weight gain. Clomiphene use is also linked to a small risk of visual disorders, but vision is often restored after the medication is discontinued. Some deterioration of semen has been found with large quantities of this drug. [5, 12].

Furthermore, in comparison with estrogens, SERMs increase the risk of phlebothrombosis just as much [3].

Some known trade names (8/2019): TADEX, TAMOFEN, CLOMIFEN.

 

Joni Askola
Master of Health Sciences (MHSc)
Dopinglinkki

 

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[9] Mazzarino M, Braganò M, de la Torre X, Molainoini F, Botrè F. Relevance of the oestrogen receptor modulators tamoxifen, toremifene and clomiphene in doping field: Endogenous steroids urinary profile after multiple oral doses. Steroids. 2011; 76(12):1400–1406
 
[10] Mattson J, Vehman L. Miehen rintasyöpä. Duodecim. 2016;132(7):627–31
 
[11] Duodecim lääketietokanta. 2019. TAMOFEN 20 mg tabl. Terveysportti
 
[12] Wheeler K, Sharma D, Kavoussi P, Smith R, Costabile R. Clomiphene citrate for the treatment of hypogonadism. Sex Med Rev. 2019;7(2):272–276


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