Oxandrolone is an androgen and synthetic anabolic steroid (AAS) used for several purposes. It helps with weight gain in specific situations, counters protein breakdown from long-term corticosteroid use, supports recovery from severe burns, treats bone pain caused by osteoporosis, and aids in the growth of girls with Turner syndrome, among other uses.

It’s known for its performance-enhancing effects and relatively low side effects compared to other steroids. It is often used by bodybuilders and women. However, long-term use of anavar can lead to negative side effects, notably depression and hypogonadism (low testosterone levels) – when run as an anavar only.

Anavar can cause hypogonadism because it activates androgen receptors in the hypothalamus, which downstream signals the body to reduce its own testosterone production. Keep in mind this occurs even though anavar does not convert to estrogen.

Metformin is a medication commonly used to control blood sugar levels in people with type 2 diabetes. If you read my article on MK-677 you would have seen it briefly discussed there.

Metformin also has anti-inflammatory effects, and I find that it holds promise in mitigating some of the negative side effects of steroids like anavar.

In my opinion all synthetic androgens are going to be neurotoxic, because there all at some level derived from Testosterone, which contrary to popular belief has been shown to be neurotoxic. The neurotoxicity of Testosterone has been shown to be minimal in the presence of estrogen, and thus aromatase, in the brain (interestingly low testosterone levels may also lead to inflammation in the brain as low testosterone levels are associated with increased pro-inflammatory cytokine expression). Following this line of reasoning the neurotoxicity of DHT-derivatives or other non-aromatising anabolic steroids is likely to be significant, particularly when run without a Testosterone base. This may be why some users report a Euphoric feeling when taking Dianabol – a highly estrogenic AAS. In this regard I don’t believe Anavar has a particularly potent neurotoxic effect compared to other AAS, it’s just that there is limited studies on AASs effect on brain health. Anavar is one of the few compounds where its neurotoxicity was investigated. 

Now before delving into the animal study its important to first that in long term studies – ‘Long-term effects of oxandrolone treatment in childhood on neurocognition, quality of life and social–emotional functioning in young adults with Turner syndrome’ of younger people with Turner Syndrome treated with Anavar, there was shown to be be no negative effect on neurocognition. However people with Turner Syndrome don’t necessarily have a neurochemistry representative of the normal population. 

There is an animal study titled ‘Metformin reduces oxandrolone- induced depression-like behavior in rats via modulating the expression of IL-1β, IL-6, IL-10 and TNF-α’, which shows that metformin can alleviate the depressive symptoms and anhedonia (inability to feel pleasure and happiness) caused by anavar, likely due to metformin’s ability to reduce the expression of pro-inflammatory cytokines, which are signaling molecules involved in inflammation.

Signs of anavar-induced brain inflammation include:

    *   Irritability

    *   Anxiety

    *   Depression

    *   Brain fog

This effect is likely related to its anti-inflammatory properties, as low testosterone levels are associated with increased pro-inflammatory cytokine expression, which can lead to inflammation in the brain.

While metformin is generally considered safe, there are some potential concerns, particularly at higher doses:

It may lower IGF-1 expression, which is a hormone involved in growth and development; however I believe the benefits of metformin outweigh this effect, especially at lower doses.

It can worsen mitochondrial function, leading to reduced responsiveness to exercise, less stamina, and faster fatigue. Again, this effect is dose-dependent and may not be noticeable at lower doses.

Testosterone replacement therapy (TRT) may be another option to consider for individuals experiencing hypogonadism from anavar use. However, it’s important to weigh the potential benefits of TRT against the potential drawback of lowering IGF-1 levels.

Cycling between different steroids can help to prevent the aggregation of side effects, but it is not a foolproof solution as most androgenic steroids can cause some degree of brain inflammation. Ultimately, taking ancillary medications like metformin may help to mitigate the negative side effects of steroids and promote overall well-being.

References:

Long-term effects of oxandrolone treatment in childhood on neurocognition, quality of life and social–emotional functioning in young adults with Turner syndrome Author links open overlay panel K. Freriks a , C.M. Verhaak b , T.C.J. Sas c d , L.A. Menke e , J.M. Wit e , B.J. Otten f , S.M.P.F. de Muinck Keizer-Schrama c , D.F.C.M. Smeets g , R.T. Netea-Maier a , A.R.M.M. Hermus a , R.P.C. Kessels b h i , H.J.L.M. Timmers a

Hammad, A. M., Ibrahim, Y. A., Khdair, S. I., Hall, F. S., Alfaraj, M., Jarrar, Y., & Abed, A. F. (2021). Metformin reduces oxandrolone- induced depression-like behavior in rats via modulating the expression of IL-1β, IL-6, IL-10 and TNF-α. Behavioural Brain Research, 414, 113475. doi:10.1016/j.bbr.2021.113475