Androstenediol: Benefits, Side Effects and Dosage

Androstenediol is a naturally occurring steroid hormone, often marketed as a dietary supplement for its supposed anti-aging, immune-boosting, and anabolic effects. But what does the science actually say about its benefits, risks, and how it should be used? Let’s dive deep into the evidence-based details of androstenediol, using clinical and experimental studies to guide our understanding.

Benefits of Androstenediol

While androstenediol is sometimes promoted for its muscle-building or testosterone-enhancing effects, research paints a more nuanced picture. Its most promising benefits are actually related to immune modulation, radioprotection, and infection resistance, rather than direct anabolic effects.

Benefit	Description	Evidence/Outcome	Source(s)
Immune Support	Enhances resistance to bacterial and viral infection	Improved survival in mice and monkeys	1, 2, 3, 4, 5
Radioprotection	Mitigates effects of radiation-induced myelosuppression	Reduced mortality, improved blood counts	2, 4, 7
Immune Modulation	Stimulates myelopoiesis & cytokine expression	Increased neutrophils, platelets, cytokine responses	2, 3, 5
No Muscle Gain	No significant effect on muscle or strength	No difference vs placebo in trials	6

Table 1: Key Benefits of Androstenediol

Immune System Enhancement

Research in animal models clearly demonstrates that androstenediol can significantly boost immune system function, especially during periods of stress or immune suppression. In mice, androstenediol improved survival rates following exposure to lethal bacterial infections, including both gram-positive and gram-negative pathogens. Its protective effects stemmed primarily from modulating the immune response, not from directly killing bacteria. Androstenediol was also shown to reduce mortality from endotoxin (LPS) challenge, suggesting it counteracts harmful inflammatory cascades 1.

Further, studies in irradiated mice and monkeys revealed that androstenediol can stimulate the production of immune cells (myelopoiesis), increasing neutrophil and platelet counts. This effect helped animals survive otherwise-lethal doses of radiation and secondary infections, due to faster recovery of the bone marrow 2, 4.

Radioprotective Effects

Androstenediol’s radioprotective properties are among its most scientifically robust benefits. Post-radiation, animals treated with androstenediol recovered bone marrow function faster, leading to improved blood counts and dramatically higher survival rates. In rhesus monkeys, for example, androstenediol reduced deaths from radiation-induced myelosuppression, even in the absence of clinical support like antibiotics or transfusions 4. These effects are attributed to the hormone’s ability to both stimulate hematopoiesis and modulate immune signaling.

Modulation of Immune Responses

Beyond simply boosting cell counts, androstenediol modulates the immune response at a cytokine level. In tuberculosis-infected mice, it promoted a favorable Th1 response (important for controlling TB), increased beneficial cytokines such as TNF-α and IL-2, and helped maintain granuloma formation (crucial for containing infection). It counteracted the immunosuppressive effects of glucocorticoids, suggesting potential utility in diseases where immune balance is disrupted 3.

In the context of viral infections, androstenediol pretreatment protected mice from lethal influenza, enhanced T-cell activation, and prevented stress-induced immune suppression 5.

Lack of Anabolic or Muscle-Building Effects

Despite its popularity in supplement culture, high-quality clinical trials failed to demonstrate any significant benefit of androstenediol supplementation for muscle mass, strength, or body composition. In middle-aged men participating in resistance training, androstenediol did not outperform placebo for any anabolic outcome 6.

Side Effects of Androstenediol

Just as important as understanding benefits is knowing the risks. Androstenediol, particularly at supplemental doses, can have notable side effects—especially concerning hormone balance and cardiovascular health.

Risk	Manifestation	Severity/Notes	Source(s)
Estrogenic Effects	Increased estrone, estradiol	Significant, dose-dependent	6, 9
Hormonal Disruption	Downregulation of endogenous testosterone	Noted with regular use	6
Cardiovascular	Reduced HDL, worsened lipid ratios	Increased heart disease risk	6, 8
Mild Toxicity	Local site reactions, weight loss	Minor in animal studies	7

Table 2: Key Side Effects of Androstenediol

Hormonal Imbalances and Estrogenic Effects

One of the most consistent findings in human trials is the conversion (aromatization) of androstenediol into estrogens. Both short- and long-term supplementation led to significant increases in estrone and estradiol levels. This is particularly concerning for men, as elevated estrogens can lead to gynecomastia, mood changes, and other unwanted effects 6, 9.

Moreover, chronic supplementation reduced endogenous testosterone synthesis, likely due to feedback inhibition at the level of the hypothalamus and pituitary. Luteinizing hormone levels dropped by up to 33%, signaling a potential for long-term disruption of natural testosterone production 6.

Cardiovascular and Lipid Effects

Androstenediol supplementation adversely affected cardiovascular risk markers in clinical trials. Specifically, it lowered HDL cholesterol ("good" cholesterol) and worsened LDL/HDL and apolipoprotein ratios, both of which are associated with increased risk of coronary heart disease. These negative effects occurred even without changes in body composition or diet 6, 8.

Safety and Toxicity Profile

Animal studies suggest that androstenediol has a fairly wide safety margin. Doses as high as 4000 mg/kg given subcutaneously or 4800 mg/kg orally resulted in very low rates of acute toxicity in mice. The most notable side effects were mild to moderate, including localized skin reactions and some weight loss at higher doses. Elevations of granulocytes in abdominal organs were also observed, likely reflecting the drug’s immune-activating properties 7.

Other Considerations

• No evidence of direct antibacterial effect: Its beneficial immune effects appear to be indirect, rather than from killing pathogens directly 1.
• Potential for immune overactivation: While not observed in the cited studies, theoretically, excessive immune stimulation could pose risks in certain individuals.

Dosage of Androstenediol

Determining the optimal and safe dosage of androstenediol is challenging, as most human data come from short-term studies focused on healthy volunteers or supplement users. Animal studies, however, provide a broader picture of effective and tolerated ranges.

Dose (mg/kg)	Administration	Effect/Outcome	Source(s)
5–160 mg/kg	Subcutaneous	Effective for radioprotection, infection resistance	2, 7
1600–4800 mg/kg	Oral (animals)	Survival benefit, low toxicity	7
200 mg/day	Oral (humans)	Increased estrogens, no muscle benefits	6
320 mg/kg	Subcutaneous	Immune boost, some local toxicity	5, 7
300 mg/day	Oral (humans)	Increased testosterone/estrogens in some, variable response	9

Table 3: Androstenediol Dosage in Studies

Animal Studies

In mouse and primate research, doses from as low as 5 mg/kg up to 160 mg/kg subcutaneously were effective for radioprotection and immune stimulation. Oral doses required were higher—up to 1600 mg/kg for significant survival benefits. Even at very high doses (4000–4800 mg/kg), toxicity was minimal, though some weight loss and local skin reactions were seen 2, 4, 7.

Human Trials

In clinical studies with resistance-trained men, the most common dose was 200 mg/day by mouth. This dose did not enhance muscle or strength gains but did increase estrogen levels and altered lipid profiles negatively 6. Another study used 300 mg/day and observed increased testosterone and estrogens in some individuals, but with considerable variability in response 9.

Practical Considerations

• No established therapeutic indication: Androstenediol is not approved for any medical use, and all human data come from supplement trials or experimental protocols.
• Supplement label doses: Commercial supplements usually recommend doses in the 100–300 mg/day range, which is within the scope of human trials but not without risk.
• Animal vs. human dosing: Effective immune/radioprotective doses in animals are much higher (per kg) than those used in humans, highlighting important species differences and caution in extrapolation.

Summary of Dosage Guidance

• For immune or radioprotective purposes: Doses effective in animals do not translate directly to humans, and there is no clinical guidance for such uses in people.
• For muscle-building/athletic use: Doses of 200–300 mg/day have no proven benefit and pose hormonal and cardiovascular risks.
• Safety: High-dose animal data suggest a wide margin, but mild side effects can occur, and long-term human safety is not established.

Conclusion

Androstenediol is a steroid hormone with intriguing effects on the immune system and promise as a radioprotective agent in animal models. However, its use in humans, particularly as a supplement for muscle gain or anti-aging, is not supported by robust evidence and may carry real health risks.

Key Points Covered:

• Immune and Radioprotective Effects: Androstenediol enhances resistance to infection and counters radiation-induced bone marrow suppression in animal studies 1, 2, 3, 4, 5.
• No Anabolic Benefit: Clinical trials show no increased muscle or strength gains compared to placebo in humans 6.
• Side Effects: Notable risks include increased estrogen levels, suppression of natural testosterone, and adverse effects on heart disease risk factors 6, 8, 9.
• Dosage: Effective doses in animals are much higher than those used in human supplements; doses of 200–300 mg/day in people impact hormones/lipids without clear benefits 6, 9.
• Safety: Animal data suggest low acute toxicity but some mild side effects; long-term human safety is unproven 7.

In summary: While androstenediol demonstrates unique immune-modulating properties in animal studies, its use as a supplement in humans is unproven for most claimed benefits and carries significant hormonal and cardiovascular risks. Anyone considering its use should weigh these factors carefully and consult a healthcare professional.