Dehydroepiandrosterone, or DHEA, is a 19-carbon steroid that is naturally produced in the body in many forms. Epiandrosterone (EA) is the base molecule and the dehydro (DH) can be in many positions which all have benefits for health and longevity. These forms of DHEA provide similar benefits to traditional 5-DHEA without some of the negatives. 5-DHEA is often too active in tissues.
When we age, our natural hormone levels change. In men this means less testosterone with more estrogen and in women it means less estrogen and testosterone. These changes cause effects in older people such as muscle wasting. A New York Times article detailed this problem. “Comparisons between age groups underline the muscle disparity: An 80-year-old might have 30 percent less muscle mass than a 20-year-old.
And strength declines even more than mass. Weight-lifting records for 60-year-old men are 30 percent lower than for 30-year-olds; for women, the drop-off is 50 percent.” New forms of DHEA can minimize this loss without the damaging effects of skewed testosterone to estrogen ratio. 5-dhea has inherent estrogenic activity (feminizing characteristics) due to its relatively high affinity as a substrate for aromatase (an enzyme that converts androgens to estrogens) and has some direct binding activity to the estrogen receptor.
Though the prefix “dehydro” in dehydroepiandrosterone implies that two hydrogen atoms have been removed and a double bond is located on the steroidal rings, 5-DHEA is the isomeric form of DHEA that is most often thought of and that is most commonly sold on the market. 5-DHEA is used as a supplement for a myriad of benefits, such as aging, depression, obesity, cardiovascular risk, and adrenal insufficiency. Furthermore, safety studies regarding DHEA have proven that long term supplementation results in no significant side effects.
Several properties, however, make 5-DHEA less desirable to certain populations. Additionally, 5-DHEA has little anti-catabolic (muscle wasting) effect and 5-dhea results in high levels of 5-alpha reduced metabolites, resulting in increased androgenicity which can bother the prostate in men and cause hair growth in women. While some estrogen is good for women, men are becoming increasingly aware that environmental pesticides and chemicals are causing massive damage to the endocrine systems by skewing the estrogen/testosterone ratio. Here are some alarming facts about endocrine disruptors (like BPA) in men:
Factsheet: Male Infertility
– The average sperm count of a North American college student today is less than half of what it was 50 years ago.
– The number of boys born with penis abnormalities and genital defects has increased by 200% in the past two decades.
– Boys have a higher incidence of attention deficit hyperactivity disorder, learning disabilities, Tourette’s syndrome, cerebral palsy, and dyslexia.
– Boys are four times as likely to be autistic.
– Damaged sperm have been linked to a 300% increase in testicular cancer – a form of cancer that affects young men in their 20s and 30s.
– The chemical industry has developed more than 90,000 man-made chemicals in the last sixty years. Eighty-five percent of them have never undergone testing for their impact on the human body.
As a result of these physiological responses from 5-DHEA, not all supplement demographics will benefit from the positive aspects of DHEA in the most efficient and desired way. Isomeric variations of 5-DHEA ,1-DHEA, and 4-DHEA, as well as derivatives of 5-DHEA ,19Nor-DHEA, have differing physiological properties and therefore can be targeted more directly to specific demographics of supplement users who seek to gain the general benefits of DHEA, such as anti-aging and improvements to adrenal insufficiency, but are looking for variations of anti-catabolic, estrogenic, and androgenic effects to help balance these endocrine-disrupting chemicals.
4-DHEA is an isomer of 5-DHEA. It is different from 5-DHEA by the position of the double bond. 4-DHEA is metabolized similarly to 5-DHEA and is theorized to have similar effects; however, due to the repositioning of this double bond, studies show it is less active as a substrate (compound to be metabolized) for the aromatase enzyme, therefore decreasing the estrogenic metabolites. Therefore, 4-DHEA would be most beneficial when similar benefits from testosterone and anti-catabolic support are desired, but there is a desire for reduced estrogenicity of 5-DHEA.
1-DHEA is dehydrogenated between C1 and C2 (double bond at the first position) and is consequently metabolized into 1-ene isomers (ene implies a double bond). 1-ene dehydrogenated steroids show no substrate activity for aromatase and consequently, 1-DHEA is not estrogenic. Furthermore, 1-ene variants act as an enzymatic inhibitor for 5α-reductase which reduces the androgenicity of the compound and would be beneficial for people with prostate problems or hair loss due to androgenic alopecia. 1-DHEA is also beneficial for people who desire anti-catabolic effects but no estrogenicity and decreased androgenicity such as those in the prostate.
19Nor-DHEA (both 4-ene and 5-ene isomers) is a demethylated derivative of DHEA where carbon-19 has been removed. 19Nor steroids show nearly zero estrogenicity, very low substrate activity for aromatization, and the capability to bind directly to the androgen receptor. In addition, the enzyme, 5α-reductase, metabolizes the compound to dehydro-nandrolone derivatives which show anti-androgenic effects. 19Nor-DHEA is therefore beneficial for individuals who desire stronger anti-catabolic effects with little estrogenicity and anti-androgenic, 5α-reduced metabolites.
The aforementioned isomers and derivatives of DHEA are still safe due to the strong metabolic similarities; and in fact, the more targeted supplementation use enables the user to tailor the effects of DHEA to their physiological needs. Women who do not wish increased androgenic effects, men who have prostate problems, or individuals seeking more anabolism can take a more person-specific DHEA supplement.