Prohormones: Benefits, Side Effects, and Alternatives

Disclaimer (Please Read). Prohormones should ONLY be used by men and women over 21 years old. Prohormones are NOT meant for children, teenagers, and pregnant or nursing women. Prohormones may be banned by certain organizations (e.g. powerlifting, bodybuilding, Strongman, and CrossFit federations) so it's your responsibility to perform due diligence and ensure compliance.

Consult your healthcare professional before using prohormones, especially if you have, or have a family history of, prostate cancer, prostate enlargement, heart disease, low "good" cholesterol (HDL), or if you are using any other dietary supplement, prescription drug, or over-the-counter drug. Do not exceed the recommended serving and use prohormones at your own risk. This article and prohormones, are not intended to diagnose, treat, cure, or prevent any disease.

Introduction to Prohormones

There are three main categories of synthetically produced compounds in the fitness community used to increase muscle mass, improve strength, and drop fat:

• Anabolic-androgenic steroids (AASs)
• Selective Androgen Receptor Modulators (SARMs)
• Prohormones

The focus of this article will be prohormones; these are precursors of a hormone, which means they're synthetically produced hormones shortened amino acid chains or a steroid which is designed to be converted into an active hormone via metabolism in the body. [1] In this article we'll discuss key terms related to, history of, popular options (banned & legal), uses of, and side effects related to prohormones.

After reading this article you should be able to make a more informed decision as to whether prohormones are right for you. Before using any supplement you should have a solid foundation of lifting experience under your belt as well as a rock-solid workout, nutrition, and rest protocol.

Key Terms

Before we delve further into this article, I want to provide you with a list and meaning of common acronyms and terms used when discussing prohormones:

• HDL - High-density lipoprotein. Also known as "good cholesterol."
• LDL - Low-density lipoprotein. Also known as "bad cholesterol."
• Serum creatinine - A blood marker indicating kidney function. [2] Out of range values may indicate underlying, serious health conditions.
• Aspartate transaminase/ aminotransferase - Aspartate aminotransferase. An enzyme found in the blood that when high, may indicate liver damage. [3]
• Serum albumin - Protein in the clear liquid portion of the blood. Low levels may indicate kidney and liver malfunction. [4]
• Alkaline phosphatase - Measured to detect liver disease and bone disorder. Increased levels indicate damaged liver cells. [5]
• Glomerular filtration rate - an estimate of how much blood passes through the tiny filters in the kidneys every minute. Levels below range indicate kidney malfunction. [6]
• Orchidectomized - Testes removed. Sometimes used as a more technical term for castrated males.
• DHEA - Dehydroepiandrosterone. Produced by the adrenal glands, gonads, and brain, making it the most abundant circulating steroid hormone in the human body. [7]
• DHT - Dihydrotestosterone. A sex steroid and androgen hormone produced in the prostate, testes, hair follicles, and adrenal glands.

History & Development of Prohormones

Prohormones, as we know them today, came as a result of initial synthesis, research, and archival of steroid compounds in the late 1950s and early 1960s. [8] Many of the steroid compounds were researched but never produced and sold, until the 1990s.

The term "prohormones" arose in popularity in the late 1990s when Patrick Arnold, an amateur bodybuilder with a chemistry degree from the University of New Haven popularized 1-Androstenedione (5-androst-1-en-3,17-dione), a steroid precursor commonly known as "Andro", in the supplement market. [9] East Germans were providing this substance to its athletes over 20 years before Mr. Arnold introduced Andro in the U.S. in late 1996. [10] Mr. Arnold was also credited with developing 4-AD and 1-AD, two other popular prohormones. [11]

Prohormones are designed to be as potent as possible, while still not considered illegal under the drug laws at the time. [9] This typically means they carry a higher risk of harsh side effects compared to AAS, but the effects on muscle building, strength, and fat loss are also lower.

The original Anabolic Steroid Control Act of 1990 defined AASs as "any drug or hormonal substance that promotes muscle growth in a manner pharmacologically similar to testosterone." [12] Since prohormones are typically steroids with an altered molecular structure, athletes have used them to increase athletic performance yet still pass drug scans for high-caliber athletic events. However, with the increasing complexity and rigidness of testing prior to an event, chemists and supplement companies have been getting creative to ensure they stay ahead of the regulatory curve.

Within the past decade or so, prohormones have been under extensive regulatory scrutiny by the United States government. On October 22, 2004, President George W. Bush signed the Anabolic Steroid Control Act of 2004 into law. This law classifies a laundry list of anabolic steroids and prohormones as Drug Enforcement Agency (DEA) Schedule III controlled substances. [13]

Schedule III Controlled substances "have a potential for abuse less than substances in Schedules I or II and abuse may lead to moderate or low physical dependence or high psychological dependence." [14] Other common examples of Schedule III Controlled Substances include ketamine and products (e.g. Tylenol) not containing more than 90mg of codeine per dosage unit. Schedule III substances cannot be sold without a medical professional's prescription.

This law defines an anabolic steroid as "any drug or hormonal substance, chemically and pharmacologically related to testosterone (other than estrogens, progestins, corticosteroids, and dehydroepiandrosterone)" and "a compound can now be classified as an anabolic steroid despite having no demonstrable anabolic effect." [12][13]

Below is a list of prohormones banned as a result of the Anabolic Steroid Control Act. This is not a closed list and includes any other compound affecting testosterone, according to the definition of an anabolic steroid as defined under U.S. law: [13]

• 1-Androstenediol or 1-AD (3,17-dihydroxy-5-androst-1-ene)
• 4-Androstenediol or 4-AD (3,17-dihydroxy-androst-4-ene)
• 5-Androstenediol (3,17-dihydroxy-androst-5-ene)
• Norandrostenediol (19-nor-4-androstenediol or 3,17-dihydroxyestr-4-ene)
• 19-Nor-4-androstenediol (3,17-dihydroxyestr-4-ene)
• 19-Nor-5-androstenediol (3,17-dihydroxyestr-5-ene and 3,17-dihydroxyestr-5-ene)
• 19-Nor-5-androstenedione (estr-5-en-3,17-dione)
• Norandrostenedione (19-nor-4-androstenedione or estr-4-en-3,17-dione)
• 1-Androstenedione (5-androst-1-en-3,17-dione)
• 4-Androstenedione (androst-4-en-3,17-dione)
• 5-Androstenedione (androst-5-en-3,17-dione)
• Androstadienedione or 1,4 AD (1,4-androstadiene-3,17-dione)
• Any salt, ester, or ether of a drug or substance listed above

While the list above seems extensive and comprehensive, it doesn't cover all prohormones on the market. Supplement manufacturers simply tinkered with a few molecules to create new compounds, which fell into the grey area of not technically being outlawed by the Anabolic Steroid Control Act of 2004.

On December 18, 2014, President Barack Obama signed the Designer Steroid Control Act (DASCA) of 2014 in to law. This law immediately banned the following steroids and prohormones: [15] [16]

• 5-Androstan-3,6,17-trione (A form of 6-oxo)
• 6-bromo-androstan-3,17-dione (A form of 6-bromoandrostenedione, an aromatase inhibitor)
• 6-bromo-androsta-1,4-diene-3,17-dione
• 4-chloro-17-methyl-androsta-1,4-diene-3,17-diol (Halodrol)
• 4-chloro-17-methyl-androst-4-ene-3,17-diol ("P-Mag" or "Promagnon 25")
• 4-chloro-17-methyl-17-hydroxy-androst-4-en-3-one (17a-methyl clostebol)
• 4-chloro-17-methyl-17-hydroxy-androst-4-ene-3,11-dione (Oxyguno)
• 4-chloro-17-methyl-androsta-1,4-diene-3,17-diol (Halodrol is listed twice)
• 2,17-dimethyl-17-hydroxy-5-androstan-3-one (Methasterone or Superdrol)
• 2,17-dimethyl-17-hydroxy-5-androstan-3-one
• 2,3-epithio-17-methyl-5-androstan-17-ol (Epistane or Havoc)
• [3,2-c]-furazan-5-androstan-17-ol (Furuza)
• 3-hydroxy-estra-4,9,11-trien-17-one
• 17-methyl-androst-2-ene-3,17-diol
• 17-methyl-androsta-1,4-diene-3,17-diol (M1,4ADD)
• Estra-4,9,11-triene-3,17-dione (Trendione)
• 18a-Homo-3-hydroxy-estra-2,5(10)-dien-17-one
• 6-Methyl-androst-4-ene-3,17-dione (Found in Methyl-1 Pro)
• 17-Methyl-androstan-3-hydroxyimine-17-ol (The One or D-Plex)
• 17-Methyl-5-androstan-17-ol (Methylandrostanol / Protobol)
• 17-Hydroxy-androstano[2,3-d]isoxazole (Androisoxazole)
• 17-Hydroxy-androstano[3,2-c]isoxazole
• 4-Hydroxy-androst-4-ene-3,17-dione (Formestane)
• [3,2-c]pyrazole-5-androstan-17-ol (Prostanozol)
• [3,2-c]pyrazole-androst-4-en-17-ol
• [3,2-c]pyrazole-5-androstan-17-o (Prostanozol)

Prohormones Benefits, Side Effects, & Dangers

In general, prohormones are marketed as offering one or more of the following benefits:

• Increased muscle mass
• Decreased fat mass
• Increased endurance
• Decreased recovery time
• Increased strength.

It's believed that upon consumption, the body converts these prohormones to steroid hormones like testosterone and DHT. [12]

Some of the most common user-reported visual side effects include:

• Acne
• Hair loss
• Breast tissue enlargement (gynecomastia) in men
• Prostate swelling in men.

Although there's debate on the optimal way to measure and determine which prohormone is best, Julius Vida suggested the concept of Anabolic Ratings in his 1969 book entitled Androgens and Anabolic Agents: Chemistry and Pharmacology. His findings showed that many prohormone compounds have a higher Anabolic Ratings than traditional orally consumed AASs.

One author suggests the Anabolic Rating is merely a guideline for estimating a compound's potential for increasing muscle mass and these ratings may not exactly correlate in a real-world setting. [8] If you've ever browsed websites and forums permitting the discussion of prohormones, you'll find a plethora of experiences ranging from not working at all to being a miracle cure-all compound. Luckily, we have a handful of studies in which researchers quantitatively examined the effects of prohormones.

In one study, 17 resistance-trained males with an average age of 23 and average body fat of 13.1% were provided with either 330mg/day of 1-Androsterone (3-hydroxy-5-androst-1-en-17-one) or a placebo sugar pill and had to complete a 16 session, structured weightlifting routine over the course of 4 weeks. After 4 weeks, those taking 1-Androsterone increased lean body mass by 6.3%, decreased fat mass by 24.6%, increased their back squat one repetition max (1RM) by 14.3%, and increased their Big 3 (Bench/Squat/Deadlift) total by 12.8%.

For comparison, those in the placebo group increased muscle mass by 0.5%, decreased fat mass by 9.5%, increased back squat 1RM by 5.7%, and increased their Big 3 total by 5.9%. [18]

Based on these findings prohormones look like an extremely effective way to drop fat and increase both muscle and strength. However, researchers probed further and examined blood work. They found those in the placebo group experienced no significant changes but those taking the prohormone saw a 38.7% drop in HDL, 32.8% increase in LDL, 120% increase in LDL-to-HDL ratio, and 77.4% increase in the cholesterol-to-HDL ratio. [18]

Increases in overall cholesterol, decrease in "good" cholesterol, and increases in "bad" cholesterol increase your risk for cardiovascular disease. Furthermore, those supplementing with prohormones saw an increases of 19.6% and 113.8% for serum creatinine and aspartate transaminase, respectively. Serum albumin, alkaline phosphatase, and glomerular filtration rate decreased by 5.1%, 16.4%, and 18%, respectively. [18]

The last five values I mentioned may look cryptic, but they're key indicators of liver function; changes in all five values indicate deteriorating liver function.

Based on the outcome of this study, the downsides may outweigh the upsides of supplementing with prohormones.

Another study examines four different compounds - androstenedione, androstenediol, norandrostenedione, and norandrostenediol. One-time doses of 200+mg of androstenedione or androstenediol appear to slightly and briefly increase testosterone and estrogen levels. [19] Elevated estrogen levels may increase a person's risk of developing prostate or pancreatic cancers. [20]

Consuming less 300mg/day of these compounds for 12 weeks had no significant effect on body composition or athletic performance. In fact, researchers found that prolonged consumption of these compounds decreased HDL. Consumption of norandrostenedione or norandrostenediol for 8 weeks also did not affect body composition or athletic performance. [19] According to these results, prohormones offer little upside and serious downsides.

A third study examined 19-norandrostenedione (4-estrene-3,17-dione/NOR) and found it binds with high selectivity to androgen receptors (which is a good thing) but is 10x less effective compared to DHT (which is a bad thing). When NOR was administered subcutaneously (injected) to orchidectomized rats, researchers found that it increased (levator ani) muscle weight but did not affect prostate, seminal vesicle, or liver weights. [21]

If you recall from my article on SARMs, ideal anabolic compounds increase muscle mass and have weak androgenic properties. The findings of this study on rats suggest NOR may be an ideal anabolic compound.

Another study examined DHEA and androstenedione (A-dione) supplementation in both men and women of various ages. 50mg of DHEA administered to men and women ages 40-70 found that women experience a 200% increase in A-dione while men experience only a slight increase in A-dione.

Upping the dosage and extending the supplementation time period did not produce additional benefit. DHEA, combined with resistance training, did not significantly increase test levels, strength, or lean body mass compared to the resistance training-only group. Once again, this study found DHEA supplementation did significantly decrease HDL cholesterol which raises cardiovascular disease risk.

In men ages 19-29, 50mg/day of DHEA did not increase test levels but did increase A-dione level. Likewise, supplementation with A-dione increased A-dione levels and only increases test levels at very high doses (200+mg). Researchers suggest this is because much of the A-dione is processed by the liver before reaching the appropriate tissues.

Consuming high doses of A-dione may also increases estradiol by over 120%, which can lead to a slew of unwanted side effects. This study provides a number of mixed reports but in general, DHEA appears to increase A-dione levels but not test levels while A-dione may inconsistently raise test levels but also raise estrone and estradiol levels. [22] It is also worth noting despite these increases in A-dione and test levels, researchers did not note any dramatic changes in muscle mass, strength, or endurance levels.

The fifth and final study examines acute and chronic effects of A-dione, Androstenediol (A-diol), and DHEA in men and women. Acute ingestion of 100mg of A-dione in men does not significantly increase free or total test levels within the acute timeframe of 6 hours, but researchers suggest most athletes consume double or triple that dosage. Even after upping the dose, test levels don't significant increase; it seems more isn't always better, especially with prohormone supplements.

This study also confirms that high doses may increase test levels in some individuals but also increases estradiol levels and luteinizing hormone (LH) levels which could negative impact hypothalamic-pituitary-adrenal-testicular function. Chronic effects of A-dione in men may slightly and inconsistently increase muscle mass and strength in men with low test levels, it's not much more effective than performance resistance training alone and less effective than using testosterone replacement therapy (TRT).

The acute effects of A-diol in men appears to significantly increase estrogen levels without positively affecting test levels. Chronic effects of A-diol in men found that it produces no significant anabolic properties, which means it won't give you that edge in dropping fat, increasing strength, or muscle mass.

The acute effects of DHEA in men appears to increase estradiol levels without affecting test levels. Chronic effects of DHEA does not appear to significantly expedite fat loss, muscle gain, or strength increases compared to resistance training alone.

When women consume A-dione it appears to increase both A-dione and test levels whereas men only experience an increase in A-dione levels. There currently isn't any research on the long-term effects of A-dione or A-diol in women, but it's safe to say it could cause masculinizing effects and a deterioration of health.

The supplementation of DHEA in women appears to increase DHEA, A-dione, test, and DHT blood levels up to 8 hours after ingestion. However, long-term supplementation only appears to significantly increase test levels but may come with a number of side effects such as acne and facial hair. [12] Once again, this analysis concludes that the side effects and dangers from prohormones far outweigh the benefits.

Based on these findings one can deduce that the risk-reward of prohormones is higher than that of natural testosterone boosters and SARMs, but lower than that of AASs. This means while you may experience moderate-high increases in strength and muscle mass and/or decreases in fat mass, you are equally as likely to experience a moderate or high number of external and/or internal side effects. Prohormones are something to USE WITH EXTREME CAUTION.

The Best Non-Prohormone/SARM/AAS Alternatives

Once you've got your nutrition, rest, and weightlifting protocols dialed-in, there are a number of non-prohormone/SARM/AAS supplement alternatives to help you drop fat, increase endurance, energy, muscle, and strength. If you're looking to increase your metabolism and drop fat, look no further than:

• Caffeine
• Yohimbine HCL
• L-Carnitine

Now that you've been armed with a slew of information on prohormones, I encourage you to perform your due-diligence and determine if prohormones are right for you. If you have any questions, comments, or firsthand experiences with prohormones, let me know is the comments section below.

References

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4) "Albumin - Blood (serum): MedlinePlus Medical Encyclopedia." National Library of Medicine - National Institutes of Health. N.p., n.d. Web. 11 Sept. 2015.
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