Understanding SERMs

Serm #1: Estrogen Receptor Modulator (SERM)

Estrogens are very important hormones in human physiology. They regulate many processes such as bone growth, reproductive function, immune system activity, and other vital functions. However, they have been known to cause some side effects including gynecomastia (increased muscle mass), acne vulgaris (acne), and hirsutism (excessive hair growth). These side effects may occur even when there is no hormonal imbalance.

The most common way these side effects appear is through a deficiency of estradiol (E2) or excess of E2. There are two types of estrogen receptors; ERα and ERβ. Both types respond to both E1 and E3 but only one type responds to each hormone. When there is a deficiency of either E1 or E3, the response from one type will not be strong enough to counteract the other. Thus, if there is too much E2 in the body, it will lead to increased levels of E2 and therefore estrogenic side effects.

If there is too little E1 in the body, it will lead to decreased levels of E1 and thus antiestrogenic side effects.

To counter these side effects and remain within an optimal range, it is important that you have a balanced level of both estradiol (E2) and estriol (E3). Both hormones are able to balance the effects of each other since while E1 is an antagonist to E2, E3 is an agonist for E2. These two hormones work together so that they can maintain a proper hormonal environment. As you may have guessed, this delicate balance becomes disrupted when a person takes a SERM.

The most common adverse effects that can occur are gynecomastia, depression, diarrhea, and erectile dysfunction. The first two are very important to monitor since they may cause long-term damage such as shortened life span or an increased risk of heart disease. There have been cases of liver damage as well.

The most dangerous side effect is the induction of estrogenic cancers. Aromatase inhibitors (AIs) are not without their own side effects. One of the most concerning is that AIs may have an adverse effect on bone density leading to osteoporosis. It is very important to increase your intake of Vitamin D and calcium when using an AI.

What is a SERM you ask?

Selective Estrogen Receptor Modulators or SERMs are drugs that act similar to estrogen in the body. They can be partial agonists, antagonist, or inverse agonists. These drugs can cause an increase in estrogen levels in the body or block estrogen receptors all together.

SERMs are commonly used to treat menopausal symptoms. The most popular SERM is tibolone. This drug can treat adverse effects of low estrogen such as hot flashes and night sweats while also treating adverse effects of high estrogen such as endometriosis. It can also be used as a contraceptive. However, tibolone has also been known to increase the risk of certain types of cancer and it can cause severe adverse effects such as blood clots, liver disease, and even stroke.

Other SERMS include raloxifene, lasofoxifene, arzoxifene, and more. Most of these drugs have similar effects to tibolone and are used in a similar manner. As stated above, SERMS do not always affect estrogen levels.

Sources & references used in this article:

Molecular perspectives on selective estrogen receptor modulators (SERMs): progress in understanding their tissue-specific agonist and antagonist actions by DM Lonard, CL Smith – Steroids, 2002 – Elsevier

Selective estrogen receptor modulators (SERMS): keys to understanding their function by JH Liu – Menopause, 2020 – journals.lww.com

Effect of estrogens on skin aging and the potential role of SERMs by S Stevenson, J Thornton – Clinical interventions in aging, 2007 – ncbi.nlm.nih.gov

The first organometallic selective estrogen receptor modulators (SERMs) and their relevance to breast cancer by G Jaouen, S Top, A Vessieres… – Current medicinal …, 2004 – ingentaconnect.com

SERMs: evolutionary chemistry, revolutionary biology by CP Miller – Current pharmaceutical design, 2002 – ingentaconnect.com

Selective estrogen receptor modulators (SERMs): mechanisms of anticarcinogenesis and drug resistance by JS Lewis, VC Jordan – Mutation Research/Fundamental and Molecular …, 2005 – Elsevier

Bioactivation of selective estrogen receptor modulators (SERMs) by TS Dowers, ZH Qin, GRJ Thatcher… – Chemical research in …, 2006 – ACS Publications

Defining the” S” in SERMs by BS Katzenellenbogen, JA Katzenellenbogen – Science, 2002 – science.sciencemag.org