Nandrolone phenylpropionate and the prostate: what the research says

The prostate is a classic androgen-dependent organ. That is precisely why the question of what will happen to the prostate arises with any androgen. Nandrolone is often called prostate-friendly because of the peculiarities of its metabolism. The editorial team checked what this claim is based on and what is actually known from research.

How androgens control the prostate

The development and function of the prostate depend entirely on androgens. In prostate cells, type 2 5a-reductase is highly active, converting testosterone into dihydrotestosterone (DHT). It is DHT that is the main androgen of the prostate: it supports the growth of the gland and the secretion of its fluid.

The evidence for this dependence is convincing: men with a congenital deficiency of 5a-reductase have an underdeveloped prostate, and drugs that block this enzyme (finasteride, dutasteride) reduce the volume of the gland in benign hyperplasia.

With age, the prostate gradually enlarges in most men. Benign prostatic hyperplasia (BPH) is an extremely common condition in older people, and androgens are a necessary condition for its development, though not the only cause.

Prostate cancer is also mostly androgen-dependent in its early stages - androgen deprivation as a method of treating advanced cancer is based on this. Therefore any androgens are contraindicated in the presence of prostate cancer, which is directly stated in the prescribing information for nandrolone products.

Nandrolone in prostate tissue

The key difference between nandrolone and testosterone lies in the product of 5a-reduction. In the prostate, testosterone is amplified to DHT, whereas nandrolone is converted into 5a-dihydronandrolone, which binds to the androgen receptor more weakly than the parent substance (Kicman, 2008).

Because of this, in tissues with high 5a-reductase activity, which include the prostate, the androgenic effect of nandrolone is relatively lower. This mechanism underlies the notion of the mildness of nandrolone with respect to the prostate.

However, there are important caveats. First, nandrolone itself is a potent ligand of the androgen receptor, and at supraphysiological concentrations it acts on the prostate directly. Second, the body's own testosterone is suppressed against the background of nandrolone, so the real-life picture is more complex than in a test tube. Third, in sport nandrolone is rarely used without testosterone.

The editorial team did not find randomized studies assessing the effect of supraphysiological doses of nandrolone phenylpropionate specifically on the human prostate. So the claim that nandrolone is safe for the prostate rests mainly on pharmacological logic and experiments, not on clinical evidence.

Benign hyperplasia and symptoms

BPH manifests as lower urinary tract symptoms: a weak stream, frequent urges, nighttime urination, a feeling of incomplete emptying of the bladder. In young men these symptoms are rare, but against the background of androgens they may appear earlier.

The prescribing information for nandrolone esters lists among its warnings the possibility of worsening symptoms in men with prostate hyperplasia and the risk of urinary retention. Such warnings also apply to therapeutic use, meaning that in supraphysiological scenarios the risk is at least no lower.

• Weakening of the urine stream or intermittent urination.
• Nighttime urination (nocturia).
• Sudden strong urges.
• A feeling of incomplete emptying of the bladder.
• Acute urinary retention - a reason for emergency care.

Any of these signs in a man using androgens is a reason for examination by a urologist. It is also important not to confuse BPH symptoms with prostatitis or a urinary tract infection, which are treated differently.

Prostate cancer: the saturation model

For decades it was believed that more testosterone means a higher risk of prostate cancer. However, a large collaborative analysis of 18 prospective studies (Roddam et al., 2008) found no link between the endogenous testosterone level in the blood and the risk of prostate cancer.

To explain this, Morgentaler and Traish (2009) proposed the saturation model. According to it, the androgen receptors of the prostate become saturated at relatively low androgen concentrations. Below this threshold, tissue growth is sensitive to androgens, while above it additional androgens barely enhance it.

Data from the randomized TRAVERSE trial on prostate safety (Bhasin et al., 2023) showed that in men with confirmed hypogonadism, therapeutic doses of testosterone did not increase the incidence of high-grade prostate cancer compared with placebo. However, this concerns the restoration of a normal level, not supraphysiological doses.

For supraphysiological use of androgens, nandrolone in particular, there are no long-term controlled data on prostate cancer. The main practical rule remains unchanged: in the presence of prostate cancer or suspicion of it, any androgens are contraindicated.

PSA and monitoring prostate health

Prostate-specific antigen (PSA) is a protein produced by prostate cells. Its level depends on the volume of the gland, inflammation, injury and, of course, cancer. Androgens can raise PSA, and androgen deprivation lowers it.

The Endocrine Society clinical guideline (Bhasin et al., 2018) recommends assessing the risk of prostate cancer before starting testosterone therapy in older men, and monitoring PSA during treatment. For people who use androgens outside medical supervision, such monitoring is often absent, and that is a problem.

Interpreting PSA against the background of androgens is difficult: a slight increase may be a reaction of the gland, or it may indicate pathology. That is why the trend matters, along with the mandatory disclosure to the doctor of drug use.

The examination may also include a digital rectal examination, prostate ultrasound and assessment of residual urine. The scope of the examination is determined by the urologist, taking into account age, symptoms and family history.

Editorial conclusions

The prostate depends on androgens, primarily on DHT. In the prostate, nandrolone is converted into a weaker metabolite, which theoretically reduces its effect but does not eliminate it.

There are few clinical data on supraphysiological doses of nandrolone and the prostate, so prostate safety is more a hypothesis than a fact. Androgens are contraindicated in prostate cancer and can worsen BPH symptoms.

PSA monitoring and examination by a urologist are especially important for older men and people with a family history of prostate cancer.

We also recommend reading our materials on nandrolone phenylpropionate and hair, on its effect on male fertility and on the metabolites of nandrolone decanoate.

References

1. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol. 2009;55(2):310–320.
2. Roddam AW, Allen NE, Appleby P, Key TJ; Endogenous Hormones and Prostate Cancer Collaborative Group. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst. 2008;100(3):170–183.
3. Bhasin S, Travison TG, Pencina KM, et al. Prostate safety events during testosterone replacement therapy in men with hypogonadism: a randomized clinical trial. JAMA Netw Open. 2023;6(12):e2348692.
4. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744.
5. Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008;154(3):502–521.
6. Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.