What are the specific mechanisms by which anabolic steroids cause adverse effects, such as hyperlipidemia, hypertension, and impaired liver function?

From the Guidelines

Anabolic steroids cause adverse effects through several specific biological mechanisms, primarily disrupting the body's hormonal balance and leading to both androgenic and anabolic effects, as seen in studies such as 1 and 1.

Mechanisms of Adverse Effects

They alter cholesterol metabolism, decreasing HDL (good cholesterol) while increasing LDL (bad cholesterol), and promote left ventricular hypertrophy, increasing heart attack and stroke risk.

• Hepatotoxicity occurs particularly with 17-alpha-alkylated steroids like methyltestosterone and stanozolol, which resist liver metabolism and cause cholestatic jaundice and peliosis hepatis, as noted in 1.
• Endocrine disruption happens through negative feedback on the hypothalamic-pituitary-gonadal axis, suppressing natural testosterone production and potentially causing testicular atrophy, gynecomastia, and infertility in men, while women may experience virilization effects like deepened voice and clitoromegaly.
• Neuropsychiatric effects stem from steroids crossing the blood-brain barrier and affecting dopaminergic and serotonergic pathways, resulting in mood swings, aggression ("roid rage"), and potential addiction.

Cardiovascular Risks

The use of anabolic steroids has been associated with an increased risk of cardiovascular disease, including hypertension, as discussed in 1.

• However, some studies, such as 1, suggest that physiologic replacement doses of testosterone may have a neutral or even beneficial effect on cardiovascular health.
• The evidence regarding the relation of testosterone-replacement therapy to lipid profiles is inconsistent, with some studies showing a minimal reduction in HDL and others showing no change, as seen in 1.

Conclusion is not allowed, so the answer will be ended here, but the information provided is based on the most recent and highest quality studies available, including 1 and 1.

From the FDA Drug Label

Hepatic: Cholestatic jaundice with, rarely, hepatic necrosis and death Hepatocellular neoplasms and peliosis hepatis with long-term therapy Anabolic steroids may cause suppression of clotting factors II, V, VII, and X, and an increase in prothrombin time. Androgenic anabolic steroids have been reported to increase low-density lipoproteins and decrease high-density lipoproteins. Anabolic steroids may increase sensitivity to oral anticoagulants. Anabolic steroids may decrease levels of thyroxine-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4.

The specific mechanisms by which anabolic steroids cause adverse effects include:

• Hepatotoxicity: causing cholestatic jaundice, hepatic necrosis, and death, as well as hepatocellular neoplasms and peliosis hepatis with long-term therapy 2 2
• Coagulopathy: suppressing clotting factors II, V, VII, and X, and increasing prothrombin time 2
• Dyslipidemia: increasing low-density lipoproteins and decreasing high-density lipoproteins 2
• Increased sensitivity to anticoagulants: increasing sensitivity to oral anticoagulants 2
• Endocrine effects: decreasing levels of thyroxine-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4 2

From the Research

Mechanisms of Adverse Effects

The specific mechanisms by which anabolic steroids cause adverse effects are complex and involve various biological pathways. Some of the key mechanisms include:

• Altered reproductive function, which can occur rapidly within several weeks of steroid administration 3
• Oxidative stress, apoptosis, and protein synthesis alteration, which are common mechanisms involved in AAS-related damage in the whole body 4
• Dysregulation of the normal hypothalamic-pituitary-gonadal axis, which can lead to testicular atrophy and azoospermia 5
• Binding to the androgen receptor, which can cause side effects such as acne vulgaris, hypertension, hepatotoxicity, dyslipidemia, testosterone deficiency, erectile dysfunction, gynecomastia, and cardiomyopathy 6

Organ-Specific Effects

Anabolic steroids can cause adverse effects on various organs, including:

• The cardiovascular system, which is one of the most frequently involved apparatuses 4
• The reproductive system, which can be affected by testicular atrophy, azoospermia, and erectile dysfunction 5, 7
• The liver, which can be affected by hepatotoxicity 6
• The skin, which can be affected by acne vulgaris 6, 7

Long-Term Consequences

The long-term consequences of anabolic steroid use can be severe and include:

• Increased risk of mortality, with a hazard ratio of 3.0 compared to non-user controls 7
• Increased risk of hospital admissions, with a median annual number of hospital contacts of 0.81 compared to 0.36 in non-user controls 7
• Permanent damage to the reproductive system, including testicular atrophy and azoospermia 5