Androstenedione: Benefits, Side Effects and Dosage

Androstenedione, often dubbed "andro," is a hormone naturally produced in the human body as a precursor to testosterone and estrogen. Marketed as a dietary supplement, especially among athletes and aging men, androstenedione promises increased muscle mass, enhanced strength, and improved vitality. But does the scientific evidence support these claims? And what are the potential pitfalls and safe practices? This article dives deep into the latest research to provide a comprehensive, evidence-based look at the benefits, side effects, and dosage recommendations for androstenedione.

Benefits of Androstenedione

Androstenedione’s reputation as a “natural anabolic booster” has made it a popular supplement for those seeking athletic performance gains or age-related hormone support. But how much of this hype stands up to scientific scrutiny?

Potential Benefit	Evidence Summary	Population Studied	Sources
Testosterone Increase	Modest or no increase in most men; some effect at high doses	Healthy and hypogonadal men	1,3,7,11
Muscle Strength	No significant improvement in healthy men; gains in hypogonadal men at high dose	Healthy, hypogonadal men	1,2,4,11
Body Composition	No added benefit over placebo in healthy men	Healthy adult men	1,2,4
Estrogen Elevation	Significant increases in estrone, estradiol	Healthy adult men	1,2,3,5,7
Androgen Receptor Binding	Binds AR, promotes myogenesis (in vitro); lower potency than DHT	Cell, animal, human models	11

Table 1: Summary of Documented Benefits and Physiological Effects of Androstenedione

Androstenedione and Testosterone: Hype vs. Reality

For healthy men, especially those with normal testosterone levels, most studies show that typical doses of androstenedione (100–300 mg/day) do not significantly elevate serum testosterone over baseline 1,2,4,5,6,7. A notable exception is at the highest tested dose (300 mg/day), where a modest increase in serum testosterone was observed in some individuals, but not all 3. In hypogonadal (testosterone-deficient) men, larger doses (up to 1,500 mg/day) can produce substantial increases in testosterone, fat-free mass, and muscle strength 11.

Key points:

• Normal, healthy men typically do not experience anabolic effects from standard doses.
• Some individual variability exists; higher doses may work in select cases, but with increased risks.

Muscle Strength and Athletic Performance

Despite marketing claims, the bulk of evidence indicates that androstenedione does not enhance muscle strength or body composition beyond what is achieved through resistance training and placebo 1,2,4,6. Even when testosterone levels rise modestly, these changes are insufficient to translate into measurable athletic gains in healthy adults.

• In hypogonadal men: High doses (1,500 mg/day) led to modest gains in muscle mass and strength, likely due to testosterone conversion 11.
• In healthy men: No added benefit over placebo, even with resistance training 1,2,4.

Effects on Estrogen Levels

A consistent finding across studies is a significant increase in estrogen-related compounds (estrone, estradiol) with androstenedione supplementation 1,2,3,5,7. This occurs due to aromatization (conversion of androgens to estrogens), a process that can counteract the intended anabolic effects and introduce potential side effects.

Cellular and Molecular Mechanisms

In laboratory settings, androstenedione binds to the androgen receptor (AR) and can promote myogenesis (muscle cell development), but with much lower potency than dihydrotestosterone (DHT) 11. These cellular effects may not fully translate into real-world athletic benefits for most users.

Side Effects of Androstenedione

While androstenedione's benefits for healthy adults are limited, its side effects and risks are well-documented. Understanding these is crucial for anyone considering supplementation.

Side Effect	Description/Impact	Severity / Frequency	Sources
Estrogenic Effects	Increased estradiol/estrone; possible gynecomastia, water retention	Common	1,2,3,5,7
Lipid Profile Changes	Decreased HDL ("good" cholesterol), increased LDL/HDL ratio, heart risk	Moderate to High	1,2,7,11
Testosterone Suppression	Down-regulation of natural testosterone synthesis (via LH suppression)	Moderate	2,7
Liver Function	Possible adverse markers (at high doses/long-term); not always observed	Variable	1,4
Prostate Health	No significant PSA changes in short-term studies	Low (short-term)	4,7
Reproductive/Endocrine	Follicular cysts, premature luteinization (animal studies, females)	Experimental/Unknown	8

Table 2: Primary Side Effects Associated with Androstenedione Supplementation

Estrogenic and Hormonal Disruptions

The most consistent side effect is an increase in estrogen compounds (estrone, estradiol), which can lead to:

• Gynecomastia (male breast tissue development)
• Water retention and bloating
• Potential mood swings and libido changes

These effects are a direct result of androstenedione's conversion to estrogens through aromatase enzymes 1,2,3,5,7.

Cardiovascular Risk: Lipid Alterations

Androstenedione lowers HDL cholesterol (the "good" cholesterol) and increases the LDL/HDL ratio, both of which are associated with higher coronary heart disease risk 1,2,7,11. These changes occur even in the absence of visible improvements in muscle mass or strength.

• Example: In one study, HDL dropped by 10% over four weeks, and risk ratios worsened by up to 10.5% 2,7.

Impact on Natural Hormone Production

Supplementing with androstenedione can suppress the body's natural testosterone production by decreasing luteinizing hormone (LH) secretion 2,7. This means that after stopping supplementation, users may experience a temporary "low testosterone" state, with associated symptoms.

Liver and Prostate Effects

Short-term studies have not consistently shown significant liver toxicity or changes in prostate-specific antigen (PSA), but long-term safety remains unknown 1,4,7. Caution is warranted, especially with higher or prolonged doses.

Other and Gender-Specific Risks

• Reproductive Health: Animal studies show that androstenedione may disrupt ovarian function in females, leading to cysts and altered hormone expression 8.
• Cancer Risk: Some mouse studies suggest that androstenedione may subtly affect liver gene expression and potentially contribute to sex-specific cancer risks, but human data is lacking 9.

Dosage of Androstenedione

With conflicting reports on effectiveness and safety, understanding appropriate dosing is critical. Most studies have focused on doses between 100 mg and 300 mg daily in healthy men, with higher doses used experimentally.

Dose Range	Population	Main Outcome	Safety Observations	Sources
100 mg/day	Healthy adults	No significant testosterone change	Mild estrogenic, lipid effects	4,5,7
200–300 mg/day	Healthy adults	Variable testosterone, high estrogen	HDL decreases, LH suppression	1,2,3,7
1,500 mg/day	Hypogonadal men	Increased testosterone, muscle gain	Marked HDL drop, estrogen rise	11
>300 mg/day	Not recommended	Data lacking, increased risk	Safety not established	1,2,3

Table 3: Dosage Ranges and Observed Effects of Androstenedione Supplementation

Typical Dosage in Studies

• 100 mg/day: No significant effect on testosterone or athletic performance in healthy men 4,5,7.
• 200–300 mg/day: May increase testosterone in some, but raises estrogen more consistently; increases cardiovascular risk via lipid changes 1,2,3,7.
• High doses (1,500 mg/day): Only tested in hypogonadal men, where it increased testosterone and muscle mass, but also increased estrogen and lowered HDL cholesterol 11.

Duration of Use

Most studies lasted from several days to 12 weeks. There is no data on long-term safety, and the risks likely increase with both dose and duration 1,2,4,7.

Special Populations

• Healthy, normotestosterogenic men: No compelling benefit, increased risks at all tested doses.
• Older or hypogonadal men: High doses may restore testosterone, but at the cost of higher estrogen and cardiovascular side effects 11.
• Women: Androstenedione is not recommended due to risk of virilization, hormonal disruption, and ovarian cyst formation 6,8.

Practical Guidance

• Do not exceed 100–300 mg/day; even at these doses, benefits are questionable and side effects are common.
• Consult a healthcare provider before use, especially if you have cardiovascular, liver, or hormonal health concerns.
• Monitor lipid profiles and hormone levels if supplementing, and discontinue at the first sign of adverse effects.

Conclusion

Androstenedione has long been marketed as a natural way to boost testosterone, muscle mass, and athletic performance. However, current evidence paints a much more nuanced—and cautionary—picture.

Key takeaways:

• Limited Benefits: Most healthy men will not experience significant increases in testosterone, muscle mass, or strength from androstenedione supplementation at common doses 1,2,3,4,6.
• Significant Side Effects: Androstenedione reliably increases estrogen compounds, suppresses natural testosterone production, and lowers HDL cholesterol—raising cardiovascular risk 1,2,3,5,7,11.
• Dosing Risks: Only high doses in hypogonadal men show meaningful anabolic effects, but with increased risk of estrogenic and cardiovascular side effects 11.
• Long-term Safety Unknown: There are no long-term safety data, and animal studies raise concerns about possible cancer risks and reproductive system effects 8,9.
• Not Recommended for Most: For healthy adults, the risks of androstenedione supplementation almost always outweigh the potential benefits.

In summary:

• Androstenedione does not live up to its performance-boosting hype for healthy adults.
• Its side effect profile is significant, especially regarding estrogenic and cardiovascular risks.
• Use should be approached with caution, medical supervision, and a clear understanding of the evidence-based risks and limited rewards.