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Nandrolone Decanoate: The Devil in Disguise?
Can You Add Deca to Testosterone in HRT?
Mark Myhal, Ph.D.*
Rick Collins, Esq.*
The steroid 19-nortestosterone (nandrolone, 19-NT), popularized in esterified form as nandrolone decanoate (ND, Deca-durabolin or simply “Deca”), is an injectable synthetic anabolic-androgenic steroid (AAS) used in the strength and fitness community for building muscle. The traditional stack, hailed by “bro science” for over 40 years, combines ND with a testosterone ester such as testosterone cypionate or testosterone enanthate. The objective of the combination is to maximize the anabolic effects while keeping the adverse effects of supraphysiological use in check. ND and its relative safety as an anabolic agent has been addressed in the clinical context (48, 49) and for non-medical (i.e., athletic performance or cosmetic) use (see, e.g., past MD articles by Llewellyn, Berg, Gwartney and Antonio at https://www.musculardevelopment.com/articles/chemical-enhancement.html).
In general, there are numerous AAS-associated side effects that are dose, duration and drug dependent. Many are minor or cosmetic (e.g., acne, hair growth) but some can be quite serious (e.g., blood lipid changes, hepatotoxicity, infertility) in both men and women. While many of these effects are reversible upon cessation of use, some are not or may result in increased morbidity and mortality (41).
Nandrolone decanoate is not a C-17 alpha-alkylated AAS. It bypasses the first pass through the liver, so it is minimally hepatotoxic. Its effects on blood lipids (mild decreases in HDL cholesterol) are like or slightly greater than that of testosterone (40, 49) and, while sometimes statistically significant, may not be clinically relevant (7). On the surface, ND appears to be at least as safe as testosterone in low to moderate dosing. (19, 48, 49).
Over the past two decades there has been a growing concern about AAS use and the heart. AAS use has been linked to acute and chronic cardiac dysfunction (systolic and diastolic), cardiac hypertrophy (enlarged heart) and acute heart failure (6, 44, 59). Despite the numerous confounding variables in the cross-sectional studies and case reports of AAS users vs. non-users, these events are real and should be taken seriously especially if one has a family history of heart disease/failure or hypertrophic cardiomyopathy (HCM).
In addition to the human data, there is a substantial body of animal literature describing the deleterious effects of ND on the cardiovascular (5, 11, 14, 42, 46, 52, 54, 61) as well as the central nervous system (11). While one might argue the dosing in some animal studies is extreme (47), resulting in blood chemistry abnormalities not observed in humans, many of the animal studies when converted to an equivalent human dose (36), are certainly within the dose range for clinical use and cosmetic enhancement. For example, dosing a rat at 10 mg/kg would equate to roughly 1.61 mg/kg in a human, not 10 mg/kg (36). However, some animal treatment protocols (in vitro cell culture or intravenous administration)(42) are simply not representative of real life administration of nandrolone in humans (intramuscular injection of oil-based esters), therefore the results of such studies are speculative.
The direct adverse effects of nandrolone on the heart appear to be mediated in large part though an increase in reactive oxygen species (ROS) (58), and can be addressed with the concurrent use of antioxidants (32, 50). An upregulation of renin-angiotensin system (RAAS) has also been implicated as a driver of adverse cardiac remodeling with AAS use (45). Dysfunction of the RAAS is associated with high blood pressure, cardiovascular and kidney conditions (https://www.news-medical.net/health/What-is-the-Renin-Angiotensin-Aldosterone-System.aspx).
If your end goal is to look like a genetically altered farm animal (male or female), regardless of what AAS and related drugs you are using, it is unlikely that your patterns of use will lead to either good health or longevity. However, it’s unclear if low to moderate doses of nandrolone are cardiotoxic when used either clinically or for cosmetic purposes. This is of particular importance with the growing use of nandrolone in combination with testosterone for hormone replacement therapy (HRT), as it is a lifelong treatment (40, 55).
Why add nandrolone to testosterone in an HRT program? The rationale includes a reduction in androgenic side effects (because nandrolone’s 5-alpha reduced form, dihydronandrolone (DHN), is a much weaker androgen than dihydrotestosterone (DHT)) in tissue that is high in the 5-alpha reductase enzyme, reduced aromatization of testosterone to estradiol, increased anabolic effects on muscle and bone, and diminished joint pain (40, 55). It’s also been suggested that nandrolone could be used to treat gender dysphoria in non-binary females who wish to avoid full virilization (13).
Taking all these considerations together, questions remain. Are the studies of abusive doses of nandrolone alone, or when combined with testosterone, relevant to its clinical use for HRT/age management or gender dysphoria, or its use in low to moderate doses for cosmetic/anabolic enhancement? What are the risks of nandrolone in these contexts, and what is its proper role? We presented four questions on the subject to a panel of well-known AAS experts, including some familiar MD columnists:
• George “Dr. T.” Touliatos, MD* (GT)
• Dan Gwartney, MD* (DG)
• Victor Prisk, MD* (VP)
• Guillermo Escalante, DSc* (GE)
• Scott “Fortitude Training” Stevenson, Ph.D.* (SS)
• Eric Serrano, MD* (ES)
• Coach Victor Black* (VB)
Caveat: This discussion does not represent medical advice and does not suggest standard of care. Their responses provide discussion and considerations for purposes of discourse only. Any discussion of dosing herein is NOT to be construed as a recommendation.
Before getting started, Dr. Stevenson asked to provide further context. Nandrolone “is indeed produced endogenously, albeit only in minute, non-physiologically relevant amounts (likely as an intermediate in the enzymatic conversion of testosterone and androstenedione to estrogens (10)), and is thus unlikely to have a primary physiological hormonal role. In other words, including it in a program of HRT would serve not to replace a physiologically relevant but deficient hormone, but rather because it offers advantages as a pharmaceutical over, for example, simply administering testosterone, the dominant endogenous androgen (28).” To aid in examining nandrolone in this context, Dr. Stevenson compiled a table to compare the effects of these two steroids on several health parameters:
Health Feature
Testosterone
Nandrolone (19-NT)
Dyslipidemia, Atherosclerosis
Improvements as HRT (16, 26, 29, 30)
Generally Neutral (22, 39) or Deleterious (21, 47). (HDL reduced @ 600mg/wk (49)]
Metabolic Syndrome
Reverses as HRT (40)
Potentially reverses (via ? muscle mass)(40)
Strength & Muscle Mass
Improves (600mg/wk)(8)
Improves (600mg/wk) (49)
Erectile Dysfunction
Possible Improvement (17)
Likely Worsens (40)
Joint Health
Improves (4)
Improves (40, 55)
So, what then is the purpose of adding nandrolone to medical HRT, to a non-medical AAS stack or to a patient assigned female at birth but seeking male gender reassignment? And what are the risks? Our panelists share their thoughts below.
1. Should there be concern about long-term cardiovascular or other organ system toxicity with nandrolone decanoate alone or when combined with testosterone for HRT, gender reassignment/dysphoria or cosmetic enhancement?
GT:I believe that the side effects are dose dependent – what differentiates a drug from a poison is often the dose. If we use nandrolone decanoate along with testosterone in a reasonable protocol, we can ensure that there are no deviations of lipids and liver labs. Personally, I use nandrolone along with testosterone under frequent micro dosing of daily intramuscular shallow shots. In this way, we ensure there are no fluctuations either on estrogens or DHT, or even DHN. Long-term (ab)use of ND could contribute to positive calcium scores since ND is known to retain calcium in renal tubules; thus it’s more likely to form calcium deposits within arteries’ endothelium. However, the scenario is far better than the atheromatic plaque, since it’s considered to be stable unlike the cholesterol plaque that can be detached and form an embolism.
DG: This question is an obvious “yes” as it would be for any other pharmaceutical-based treatment, particularly using non-endogenous analogs (recognizing that nandrolone is present in trace to minor concentrations in the human system). Androgen treatment has certain risks, and that topic is far too broad to discuss here. Relative to cardiovascular, there are atherogenic issues, hypertension, cardiomyopathy (often due to an amplification of ischemic or hypertensive cardiomyopathy) subendocardial fibrosis, prothrombotic conditions, and effects of metabolites or suppression secondary to androgen use. Nandrolone is not well studied in this regard as a monotherapy in therapeutic doses, let alone in combination or at near-physiologic to supraphysiologic concentrations. Arrhythmias are another issue little regarded that are being noted anecdotally.
Vasodilation, change in compensatory hormones, hormone ratios, interaction with “other class” receptors (e.g., mineralocorticoids, estrogen, progesterone) and potential neurosteroid effects have little human research. Gender reassignment is a vastly different topic, and findings in cis-gender subjects should not be conveyed to those pursuing gender reassignment.
VB: In my opinion the principal concerns over heart health in this specific consideration are dosage dependent, and all AAS once introduced at supraphysiological range represent the same relative risk with due regard to cardiac remodeling and blood pressure elevation regardless of the derivative (type of AAS) in question. Further, these risks can be mitigated by the suppression of angiotensin II, the effector molecule of the renin-angiotensin system. This can be achieved through the prophylactic application of an ARB or ACE-i. Estrogen is considered cardioprotective, and I would not recommend a full replacement strategy with nandrolone, but the addition of some nandrolone IMO is a different risk profile for we maintain the protective underpinning of the estrogen ratio from the drug combination.
GE: As with use of any type of drug, there should always be concern for potential health risks. Every drug, no matter what it is (even over-the-counter drugs), has risks and potential side effects associated with it. Furthermore, individuals may respond differently to the same drug and the same dosage of the drug. Thus, although using the results of clinical trials to help make decisions as to what drug to use and how much to take is a good starting point, an individualized approach to treatment is prudent. One cannot completely rule out long-term cardiovascular or other organ system toxicity with nandrolone decanoate alone (not something I recommend) or when combined with testosterone for HRT, but frequently there is a dose response relationship and a length of exposure relationship before problems appear. Hence, working with a qualified physician to review signs/symptoms of health issues along with blood work and the desired outcomes, it is likely that a relatively safe dosage can be prescribed to minimize these risks. The key is to keep monitoring health markers on a regular basis (3-4 times a year) and check in with your prescribing physician to ensure everything is in check. If modifications to the plan need to be made, they can be made sooner rather than later.
SS: Yes, I would say so. Using accepted animal-to-human dose conversions (36), studies of rabbits suggest cardiotoxicity at a dose of ~600mg/wk, but not ~200mg/wk (61), whereas rat studies suggest that more reasonable weekly doses of ~100mg (1, 50) and higher human-equivalent doses [~400mg/wk(41)] are indeed cardiotoxic, possibly by creating free radical stress and/or impairing the upregulation of free-radical quenching enzymes in cardiac tissue (12).
VP: Nandrolone in combination with testosterone replacement (at a 50:50 blend) can be appropriate in two conditions. One, when regular dosing of testosterone results in adverse androgenic side effects like excessive acne or hair loss. Two, when a patient’s excessive joint pain or arthritis limits them from staying active. A recent pilot study by Tatem et al. (56) supports what readers of Muscular Development have heard for years: ND helps joint pain. The use of nandrolone for osteoporosis and other medical conditions has not shown significant adverse cardiovascular events. All the studies that I have seen in animals have been at excessive dosing and without management of testosterone levels, estrogen, or DHT as we would do in humans. Further, case reports and case series of anabolic steroid users almost always fail to mention the ancillaries (i.e., tamoxifen, clenbuterol) used by bodybuilders or C-17 alpha alkylated compounds (i.e., stanozolol) that most certainly lead to adverse cardiovascular events.
ES: I don’t believe that nandrolone is as damaging to the heart as some might believe. Most of the cardiotoxicity data comes from bodybuilders using extreme dosing and practicing polypharmacy that involves consuming a number of AAS and other drugs (stimulants, GH, possibly recreational drugs, etc.) together.
In human subjects, it has never been shown that nandrolone causes fibrosis of the heart as far as I know, only in animals using high dosages. In addition, they use GLS measurements that is the elasticity of the heart based on PATHOLOGICAL heart disease, not in normal athletic hearts.
When properly dosed, combined with testosterone and with medical supervision, nandrolone is a good anabolic steroid, even in women for improving bone density while demonstrating low androgenicity.
As a physician I always have concerns any time I prescribe medications for any reason, but the risks associated with medically supervised nandrolone use are low in otherwise healthy subjects.
2. Could the concurrent use of antioxidants like vitamin E or black seed extract (used in animal studies) mitigate, at least in part, the increase in ROS?
GT: Personally, my preventative protocol for HRT includes compounds such as niacin, resveratrol, policosanol, red rice yeast, krill oil and phytosterols. We can include Q10 that helps with energy production in the mitochondria of cells in the myocardium, along with l-carnitine that also enhances all beta oxidation of fatty acids and energy production in the myocardium. We know that the heart utilizes fat as a primary fuel under resting conditions.
DG: There may be measurable differences, but whether or not this would result in a clinical benefit or protection is unknown, and at the concentrations being used in the audience relevant to this medium, unlikely to offer significant benefit. Certain medications may have a role, and certainly there is no significant consequence to including antioxidants such as named above, or other nutritional support such as NAC or TUDCA other than the risk of a false sense of security. Protective measures would be wise, but do not mitigate the fact that a practice with potential, possibly innate risks, are being followed.
VB: Without question, yes. The challenge, however, remains: so which antioxidant and at what dosage? A polypharmacy approach or monotherapy? IMO this is the very much speculative.
GE: These antioxidants have shown some promise, but their effects and applications require further clinical and animal studies. This is especially true as it relates in their concurrent use with nandrolone. The good news is, there is little to lose in trying out these antioxidants and seeing how they work. However, this should be done in conjunction with the physician prescribing the nandrolone decanoate so that blood work and overall health can be monitored along with the effectiveness of these antioxidants.
SS: Yes. In the above-noted rat studies employing HRT-level doses (~100mg/wk human equivalent), very large intakes (2) of vitamin E (human equivalent of >5000IU/day) (50), as well as more moderate doses of black seed extract (Nigella sativa; human equivalent of ~1g/day) reversed the free radical-induced cardiotoxicity caused by nandrolone administration.
However, mega-dosing antioxidants (e.g., 400IU of vitamin E + 1000mg ascorbic acid) (37) impairs the hormetic signaling vital for the most basic adaptive responses to exercise in skeletal muscle (60), including improvement in post-exercise insulin sensitivity, and perhaps even the coveted strength gain and muscle growth evoked by resistance training (34). Thus, remedying nandrolone cardiotoxicity with antioxidants could also negate some of the important (anti-aging) health benefits of physical exercise (15).
VP: Antioxidants in the vegetables that we should be eating are great at mitigating the destructive effect of ROS. We need to listen to Hulk Hogan and, “Eat your vegetables!!!”
ES: I haven’t seen or know of any study where nandrolone was combined with an antioxidant in humans. Based on the antioxidant literature however, I would say possibly and I would use other supplements in addition to vitamin E such as zinc, magnesium, B vitamins, taurine, and fish oils. But the best solution here would be concurrent aerobic training to offset concentric hypertrophy of the heart.
3. Would the concurrent use of an ACEi or ARB reduce the risk of potential long-term cardiac dysfunction via ANG II when taken with nandrolone or AAS in general?
GT:As a matter of fact, I’m using Losartan to avoid hypertension from nandrolone use. We know that nandrolone stimulates aldosterone from the kidneys that in turn will retain sodium and water, which is fundamental in the increase in blood pressure. Therefore, taking Losartan can prevent hypertension that could lead to left ventricular hypertrophy. Moreover, it will prevent to a degree erythrocytosis out of testosterone/nandrolone use. Now, cardiovascular exercise is really important for cardiac remodeling in order to improve systolic and diastolic blood pressure. As a matter of fact, cardiovascular exercise lowers blood pressure, unlike lifting weights that increases it.
DG: There is a scientific rationale behind this that is sound, and one could certainly find support for the logic in providing prophylactic measures, ACEi likely being more beneficial than ARB, if tolerated. The burden then lies on the prescriber to ensure and monitor that the individual does not have or develop contraindications to use of these classes of antihypertensives, (e.g., declining kidney function).
VB: These risks can be mitigated by the suppression of angiotensin II, the effector molecule of the renin-angiotensin system. This can be achieved through the prophylactic application of an ARB or ACE-i.
GE: There is strong evidence to suggest that there is a relationship between androgens and the renin-angiotensin system and its effects on things such as cardiac hypertrophy, prostate hypertrophy, and mean arterial pressure. This being the case, it appears that concurrent use of ACEi or ARB may be beneficial when taking nandrolone decanoate and/or other AAS. As stated previously, this should be done under the care of the physician so that blood work and overall health can be monitored along with the effectiveness of the ACEi or ARB.
SS: Again, we have limited animal data(45) suggesting that an ARB (Losartan) can remedy adverse cardiac remodeling (excessive collagen infiltration) caused by 19-NT (~100mg/wk human-equivalent dose). [Relatedly, the data suggesting exercise can prevent adverse cardiac changes associated with 19-NT administration is equivocal (23, 56).]
VP: During my research fellowship at the University of Pittsburgh, my team researched the effects of Losartan on skeletal muscle fibrosis after injury. The data was promising with regards to better healing and regeneration of skeletal muscle. This seems to be through mitigation of TGF-?1, which has a role in models of cardiac fibrosis and hypertrophy. Those on AAS and many on TRT have issues with polycythemia and elevations in blood pressure. I often recommend Losartan as an option for lowering blood pressure due to its potential benefit to cardiac and skeletal muscle.
ES: ARBs or ACEi might offer some protection but I don’t think enough as a standalone treatment. Again the best mitigation strategy would include consuming a balanced diet that is rich in antioxidants combined with aerobic exercise to maintain healthy blood pressure and reduce systemic inflammation from excess body fat.
4. If nandrolone is used in HRT, either in combination with testosterone (or in its place), what ratio would be optimal and what would be the maximum dose mg/kg/wk for long term use?
GT:Usually, when we combine testosterone along with 19-nor derivatives that have progestational activity (trenbolone and nandrolone), we keep the ratio 2:1 between testosterone and those compounds. Personally, I’m using 25 mg of testosterone every day along with 5 mg of nandrolone decanoate every day; that makes a total of 175 and 35 respectively on a weekly basis. When I blast, my protocol is adjusted to 250 T per week along with 50 ND per week. Of course, I could go higher on ND, but I want to avoid bloating and edema and perhaps an HDL dropping along with an elevation in hemoglobin. Besides, the pharmaceutically prescribed doses for nandrolone refer to up to 100 mg per week for anemia, osteoporosis and muscle wasting.
DG: Again, with the caveat that this is for the purposes of discussion, not medical advice, condoning or providing guidance or support for such practice, there is again reason one might utilize a combination of nandrolone with testosterone. This relates not only to the direct effects (genomic and non-genomic) of the relative androgens, but also to that of the metabolites. The primary focus is on relative androgenicity, with the metabolite of nandrolone via the 5-alpha reductase enzyme being DHN noted to be about one-third to one-quarter that of DHT, the 5AR metabolite of testosterone. Focusing on this, some have come to follow a practice that is not novel, of following a ratio of 2:1 to 4:1 testosterone:nandrolone. The logic being that in target tissue (e.g., prostate) the nandrolone metabolite DHN would compete with DHT and reduce the androgenic stimulation in tissues with high 5-alpha reductase activity associated with certain adverse effects (e.g., hair loss, prostate hypertrophy). It is possible it may also mitigate mood disruption as T supplementation has a greater relative positive effect (making it more likely to happen) on provoked aggression. Nandrolone supplementation is neutral relative to eugonadal (normal) testosterone levels (regarding mood effect). However, people fail to realize that there is no research on the 5AR activity in the general population. Given that nandrolone is actually three times more androgenic that testosterone (relative to binding to the androgen receptor), this could explain why some have erectile dysfunction with nandrolone, while others experience no erectile dysfunction but do experience hair loss. I have approached university departments with interest to collaborate on studies but with no response. Female athletes frequently experience male pattern hair loss, clitoral enlargement and voice deepening with nandrolone. Another issue lies in the estrogenic/progestenic risk and feminizing side effects (e.g., gynecomastia), which again require more time and space than this allots. (I don’t provide dosage discussion.)
VB: The only clinical evidence that we have to support this discussion is in the Tatem et al. study (63) cited in the reference materials and I feel these ratios are supported in observation as well. A final note: I would like to see a head-to-head study comparing the efficacy of nandrolone and Anavar (oxandrolone) in this application, for there is some evidence to suggest it may be a suitable candidate in this role via an alternative pathway. And since DHT derivatives may well have a different safety profile regarding brain health, it may be worthy of further investigation (63).
GE:Nandrolone decanoate dosage typically begins at about 100 mg/wk and can go up to 200-400 mg/wk for more performance enhancement goals. In a six-month intervention using nandrolone decanoate in patients undergoing dialysis for 6 months, 100 mg per week had a significant increase in lean body mass and the drug was generally well tolerated (25). In terms of long-term use, lower dosages typically minimize health risks. Nandrolone decanoate complements testosterone well and the combination of the 2 drugs can mean lower dosages of each. A starting point might be a ratio of 1:1 to 1:2 ND to testosterone ester using lower dosages of each. Thus, instead of using 400 mg/wk of ND, a more conservative approach could be to use 100 mg/wk of ND along with 200 mg of testosterone ester per week. Of course, a licensed physician should determine an ideal dosage based on individual needs and health. Furthermore, regular check-ups and blood work should be performed to monitor the effects of the intervention.
SS:Based on the scientific literature I'm aware of (as I'm not a physician who can legally prescribe hormone replacement therapy and may have personal clinical evidence to the contrary), nandrolone seems to offer little advantage generally speaking over testosterone alone or as an adjunct to a medically supervised program designed to replace/restore testosterone levels for the purpose of optimizing quality of life and improving adverse outcomes of hypogonadism or gender reassignment. As follow-up on the Table and responses above, the following are worthy of note:
• Nandrolone may worsen or precipitate erectile dysfunction by interfering with conversion of testosterone to dihydrotestosterone and/or disrupting the testosterone/estrogen balance (40, 51).
• Animal data suggest that 19-NT-induced cardiotoxicity could be minimized by quenching free radicals, and that an ARB might protect against unwanted cardiac remodeling, but prescriptive recommendations would be premature without supportive human clinical trials, especially given the negative effects of antioxidant (mega-dosing level) supplementation on exercise adaptation (see above). Black seed extract has impressive neutraceutical potential...
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