Dehydroepiandrosterone

Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone. It is one of the most abundant circulating steroids in humans, where it is produced in the adrenal glands, the gonads, and the brain. DHEA functions as a metabolic intermediate in the biosynthesis of the androgen and estrogen sex steroids both in the gonads and in various other tissues. However, DHEA itself possesses weak androgenic activity.

Production and Regulation

DHEA is produced from cholesterol through two cytochrome P450 enzymes. First, cholesterol is converted to pregnenolone by CYP11A1. Pregnenolone then serves as a precursor for DHEA, being converted by CYP17A1 enzyme. The production of DHEA in the body reaches its peak in the mid-20s, after which it steadily declines with age. This decline has led to the interest in DHEA supplementation as a way to counteract aging processes.

Functions

While DHEA has weak androgenic effects itself, it serves predominantly as a precursor to more potent androgens such as testosterone and dihydrotestosterone (DHT), as well as to estrogens like estrone and estradiol. It is thus involved in the development and maintenance of secondary sexual characteristics, bone density, muscle mass, and other physiological functions.

DHEA also has been shown to have effects on the immune system, possibly contributing to its role in disease resistance. It may enhance cognitive function and provide protective effects against certain conditions such as osteoporosis, type 2 diabetes, and cardiovascular diseases, although more research is needed to fully understand these relationships.

Clinical Use

DHEA supplementation has been explored for various clinical applications, including the treatment of adrenal insufficiency, depression, and systemic lupus erythematosus (SLE). However, its effectiveness for these conditions remains controversial, and its use is not universally endorsed in clinical practice.

Risks and Side Effects

The supplementation of DHEA can lead to several side effects due to its conversion to more potent androgens and estrogens. These can include oily skin, acne, hirsutism, and changes in menstrual cycle in women, and increased risk of prostate hypertrophy and cancer in men. Long-term effects and safety of DHEA supplementation are not well understood, and it is recommended to proceed with caution.

Regulation

In many countries, DHEA is available as a dietary supplement, but its sale and use are more strictly regulated in others due to potential health risks and performance-enhancing effects. The World Anti-Doping Agency (WADA) includes DHEA on its list of prohibited substances for athletes.

Conclusion

DHEA plays a crucial role in human physiology as a precursor to sex steroids and has potential therapeutic applications. However, the benefits and risks of DHEA supplementation need to be carefully weighed, and more research is necessary to fully elucidate its effects.

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  Dehydroepiandrosterone structure

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  Dehydroepiandrosterone molecule ball model

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  Steroidogenesis pathway