Anabolic/androgenic steroids display a wide range of physiological effects. Androgen receptors are found in numerous body tissues including skeletal muscle, skin, scalp, liver, heart, prostate, brain and nervous system, bone, adipose and kidney tissue, and consequently these drugs, as our endogenous androgens, have numerous activities in the body aside from just building muscle. Although often misunderstood, many are well discussed. One topic however is rarely spoken about aside from passing mention, namely that anabolic/androgenic steroid can have a positive effect on red blood cell production. Red blood cell concentrations are of course integral to the oxygen carrying capacity of the blood, and increased production could possibly have numerous related benefits. You probably know of this link, however I thought many of you might wish to delve into the underlying mechanisms involved, as well as the physiological differences between anabolic agents in this regard.
Androgen Action in the Kidneys
Androgen receptors located in the kidneys are responsible for augmenting the stimulation of red blood cell production, or more specifically the process or erythropoiesis. They of course only play a supportive role; otherwise androgens would be essential to blood oxygen carrying capacity and life function, which they are not. Their role however remains significant. Men and women for example display notable variances in red blood cell content, with men carrying a much higher concentration of red blood cells in comparison. As follows, castration of the male testicles (eliminating testosterone production) will result in an approximate 10% drop of red cell mass, as well as a decrease in red blood cell diameter and life span. Women given therapeutic doses of testosterone similarly notice an increase in the concentration of hemoglobin of about 43g/l, and hematocrit increases by about 11%. Although not the key regulators of this process, we can see that androgens clearly influence the rate of erythropoiesis in humans.
The exact process of erythropoiesis appears somewhat complex, as do most body functions when under examination. Red blood cells begin as immature and physically undetermined stem cells, which reside in the bone marrow waiting to be called upon by the body for various blood and lymph system uses. In the case of red blood cells, the renal hormone erythropoietin is the signal that tells the bone marrow to form these cells from stem cells. They will develop first into a series of immature precursor cells, and ultimately adult red blood cells. The normal stimulus for the production and release of erythropoietin is hypoxia, or a lower than ideal supply of oxygen to the body tissues. High red blood cell concentrations alternately serve as a feedback mechanism, lowering the release of erythropoietin so that RBC concentrations to not get over elevated. Androgens are known to primarily act at the level of erythropoietin, enhancing the release of this hormone from renal tissue. It is also suggested however that androgens may affect the stem cell directly, perhaps by enhancing cell responsiveness to erythropoietin.
RBC Concentrations and Performance
If we would like to look at the performance enhancing effects of altering red blood cell concentrations, the most obvious group to focus on are endurance athletes. Blood oxygen carrying ability is inextricable to a person’s capacity for endurance exercise, so athletes in this area above others are aware of the methods and benefits of enhancing red blood cell concentrations. Endurance athletes for instance have made the practice of blood doping infamous. This procedure involves the removal and storage of blood cells, which are infused back into the body within one week of competition time. The athlete is given enough of a window (usually 5 to 6 weeks) to replenish the earlier withdrawn cells, so this infusion works to increase the overall concentration of red blood cells above what the body would produce normally.
A typical blood doping procedure as outlined can increase performance considerably. Figures using 750ml of packed red blood cells for example show a 26.5% increase in hematocrit (the ratio of the volume of packed red blood cells to the volume of whole blood) and an increase in the maximum oxygen uptake capacity of 12.8% after the procedure. In such a state it is easier for the body to transport oxygen to various tissues, enhancing aerobic capacity and endurance, and reducing submaximal heart rate and blood lactate buildup. Many have sworn by this method over the years, believing it to be the difference between winning and losing on many occasions. With the expected improvement in oxygen carrying capacity usually measuring between 5% and 13% in increase, we can certainly see why.
Anabolic and Erythropoietic Potency
Bodybuilders of course could usually care less about blood doping, however we do occasionally make note of the fact that steroids do enhance erythropoiesis. Although you most often hear talk of heightened RBC production with Anadrol and Equipoise in particular, this effect is not unique to these drugs. In fact all anabolic/androgenic steroids share this ability to one degree or another, usually in direct proportion to the anabolic capacity of the compound. This is due to the fact that the kidneys share a similar enzyme distribution to the muscles, namely high levels of 3alpha-hydroxysteroid dehydrogenase enzymes and little 5alpha-reductase. These two enzymes are the primary force in the disassociation of the androgenic and anabolic properties of various compounds, as they serve to alter their activity in specific target tissues. Renal tissue therefore respond to androgen stimulation on a very similar level to muscle tissue.
Poor anabolics such as dihydrotestosterone and Proviron, which are highly susceptible to 3HSD deactivation in the muscles, are also poor promoters of erythropoiesis. Potent anabolics such as nandrolone, testosterone and oxymetholone are similarly good enhancers of erythropoiesis. Since most steroids outside of DHT and Proviron are at least moderately potent anabolics, they should therefore also be relatively effective at increasing red blood cell concentrations. In clinical trials often there is no advantage reported with one agent over another, even in head to head simultaneous comparisons. For example, a study looking at the effects of oxymetholone, methenolone and drostanolone in 69 patients with aplastic anemia noted a group remission rate of 48%, with no therapeutic advantage being noted with any particular compound. Stanozolol, norethandrolone and methandrostenolone are also shown to produce a similar remission rate of about 50% with patient suffering from the same condition, with again no known advantage being apparent in any. Testosterone, ethylestrenol, nandrolone, fluoxymesterone and methyltestosterone have similarly also demonstrated a marked effect on erythropoiesis, with therapeutic potential.
And we need not look only at clinical patients with renal deficiencies to see a positive effect. A study in the British Journal of Sports Medicine for example followed the hematological effects of steroid use in a group of 5 power athletes over a period of 26 weeks, and compared them a control group of 6 non-using men. During this study an average increase of 9.6% was noted in hematocrit values in the steroid using athletes, compared to no change in the control group. The change in hematocrit of course was far from the mark that was recorded with the mechanical blood doping procedure, yet it is still an elevation worthy of note. We did however not see an overall positive change in this study that would be indicative of enhanced aerobic performance, due to the fact that hemoglobin (the pigment agent of red blood cells responsible for the transport of oxygen) levels did not rise significantly enough. Another study published in the same journal noted better results though, this time looking at the effects of long-term methandrostenolone treatment on six bodybuilders. The dosage used was a maximum of 20mg per day, which the subjects had taken in intermittent cycles for a year or more. Investigators reported increases in both hemoglobin and hematocrit, which were quite elevated in one subject in particular. Although not directly looking at maximum oxygen uptake capacity, these studies do make evident, at least the possibility, that anabolic agents might enhance aerobic capacity under the right conditions.
Although clearly not as effective as mechanical blood doping, or even the newer practice of erythropoietin injections, anabolic/androgenic steroids still do enhance Red Blood Cell concentrations. Whether or not this will consistently equate into an increase in aerobic capacity in healthy athletes remains a matter of speculation and debate, however their base effect on the process of erythropoiesis does not. Since bodybuilders are rarely concerned with things such as overall oxygen uptake capacity and optimal aerobic performance, no doubt this debate is not of tremendous interest to the average reader. Perhaps of greater interest though is the simple understanding of the mechanism involved in erythropoiesis, and how anabolic steroids interact with this process. I hope also evident through this piece is the more primary focus on the different agents, and the fact that the enhancement of red blood cell production is a trait shared by all anabolic/androgenic steroids. Certainly those mentions of the vast superiority of one agent such as Anadrol or Equipoise over all others should be ignored.