S4 Hormone and metabolic modulators


Substances classified as «hormone and metabolic modulators» modify the effects of hormones or accelerate or slow down specific enzyme reactions. For example, anti-oestrogens can block the conversion of the male sex hormone testosterone into the female sex hormone oestrogen.


Hormone and metabolic modulators are substances:

  • which influence the hormones and thus modify their effects;
  • which act on the body's metabolism.

Hormone and metabolic modulators have been prohibited as doping agents in and out of competition since 2001 for men and since 2005 for women.

Introduction: Anti-oestrogens

Aromatase inhibitors, Selective Estrogen Receptor Modulators (SERMs) and other substances listed under S4 are summarized as anti-oestrogens. These substances are not primarily used by athletes to enhance performance but rather to suppress the adverse effects of anabolics abuse.

Introduction: Myostatin inhibitors

Aside from anti-oestrogens, myostatin inhibitors also belong to the class of hormone and metabolic modulators. Myostatin is a protein produced by the human body. It inhibits muscle growth and thus prevents the muscles from growing in an uncontrolled way. Inactivation of the natural protein function of myostatin leads to excessive muscle growth.

Introduction: Metabolic modulators

  1. Insulin (discussed separately in the module «S4 Insulin»).
  2. Agonists of the peroxisome proliferator-activated receptor δ (PPARδ) (e.g. GW1516) and agonists of the PPARδ-AMP-activated protein kinase axis (AMPK) (e.g. AICAR).

Improving endurance performance is one of the most influential factors in modern sports. Whether this be through training and diet or through drugs and doping. In pharmaceutical studies, for example, AICAR and GW1516 have shown excellent properties for increasing endurance performance. Both substances modulate a receptor called PPAR delta, which is located predominantly in fat tissue and plays an important role in the body's energy balance. The substances AICAR and GW1516 have not (yet) been developed to the point of marketability as medicines, but have already found their way on to the black market.

Effect of hormone and metabolic modulators

The class of hormone and metabolic modulators comprises a variety of substances that modify the effects of hormones, either by blocking or stimulating receptors, or by boosting or inhibiting specific enzyme reactions.

An anti-oestrogenic effect can be achieved in two basic ways:

  • So-called aromatase inhibitors inhibit the enzyme aromatase which converts testosterone into oestrogen.
  • By contrast, selective oestrogen receptor modulators (SERM) bind to oestrogen receptors and thus block the effects of oestrogen.

In the body, anabolics are partially converted into oestrogen. Administered anti-oestrogens weaken the effect of oestrogen, either by inhibiting aromatase enzymes which convert testosterone into oestrogen or by antagonistically blocking the oestrogen receptors.

⬇ Oestrogen effect

Side effects and consequences of anti-oestrogen abuse

Anti-oestrogens have a wide range of unspecific adverse effects. The potential for adverse effects varies among the substances and includes, among others, hot flushes, fatigue, skin rashes, vaginal bleeding, abdominal pain, nausea, headache, dizziness and visual disturbances. Occasionally, an increased risk of thrombosis has been observed.

Moreover, hormone and metabolic modulators interfere with the endocrine system (glandular system) of the body and thus increase the risk of severe illnesses.

Affected sports

Hormone and metabolic modulators with anti-oestrogenic effect are used to prevent the adverse effects of anabolics. As a result, abuse occurs in the same sports where anabolics are also abused. Hence, strength and combat sports such as weightlifting and boxing as well as endurance sports such as cycling and cross-country skiing are affected. The most widespread abuse occurs in the body building scene. This is precisely the domain where anabolics are often taken in large doses.