Androgenic hormones such as testosterone and anabolic steroids (as well as prohormones) have long been used by athletes for their effects on increasing muscle mass and strength. The anabolic effect on muscle is certainly not the only physiological effect that these hormones possess however, and for many people not particularly interested in bigger muscles androgens might offer other special benefits that justify their usage. Specifically, these involve improvement in the overall psychological state, and optimization of the libido and sexual function.
Testosterone is the primary androgenic hormone. It instills its effects on the body both directly, and through its conversion to metabolites (DHT, estradiol etc). Androgens and other steroid hormones primarily exert their direct activities through binding to specific receptors present in the cytosol of cells. Upon binding to the receptor, the hormone forms a complex that then travels to the nucleus of cells where it interacts with DNA to promote the formation of specific proteins that then direct the actual biological changes.
Within the central nervous system (CNS), androgen receptors are heavily located in specific places. Androgens and other steroid hormones are able to penetrate the blood brain barrier and interact with their appropriate CNS cytosolic receptors. The hypothalamus and anterior pituitary gland are particularly dense in androgen receptors, and here they help regulate the secretion of androgens as well as other hormones that control a wide variety of biological functions. Androgen receptors are also located in parts of the cerebral cortex, medulla, and amygdala. Here their specific functions are not as well characterized.
The processes of androgen action that involve receptor binding and DNA translation are known as receptor mediated, or “genomic”, hormone actions. However, there are also lesser known actions of steroid hormones that are non-genomic in mechanism. Non-genomic activities are particularly key in the central nervous system where they combine with genomic activities to produce specific effects.
Non-genomic actions of steroid hormones differ in a very important way from genomic actions. Genomic effects are manifested over a relatively long period of time (days) because they require a complex cascade of events (binding, translation, transcription, accumulation of active enzyme products) before the actual physiology of the target organ is altered. On the other hand, genomic actions are extremely rapid (<1 minute). They are rapid because their effects involve an immediate modulation of the membranes of cells (particularly neural cells). These modulations may include changes to the permeability of the membrane, as well as effects on the opening of vital ligand gated ion channels. The end result is a quick and significant influence upon the activities of key areas of the brain, and the relevance of this to the medicinal use of androgenic hormones or prohormones should not be overlooked.
So far I have briefly covered the basic mechanics of androgen activity in the central nervous system. However, one very important aspect of this has yet to be covered, and this concerns the “activation” of androgens at the CNS targets by enzymatic metabolism. Specifically speaking, the conversion of testosterone to its two most powerful metabolites; dihydrotestosterone (DHT) and estradiol.
One thing most people do not realize is that although testosterone is an active hormone, its primary function in some of the most vital areas of the body and the brain is as a prohormone. There are locations all over the CNS that are rich in 5 alpha-reductase, or aromatase, or both; in particular areas of the CNS that involve libido. It is in these areas that testosterone must first be converted to fully carry on its message.
5 alpha-reductase is found in high concentrations in various parts of the brain, particularly in the white matter. It is localized specifically in the myelin (outer fatty sheath of neurons). 5 alpha reductase (5-AR) converts testosterone into DHT, which is a much more potent androgen than testosterone. As a result, the androgenic signal of testosterone is “amplified” in 5-AR rich tissues. The significance of 5 alpha-reduction to the psychosexual actions of testosterone is made depressingly evident to many individuals that take finasteride (Proscar, Propecia) for prostate hypertrophy or male pattern baldness. In a considerable portion of these individuals a loss of libido and sexual function is experienced as a side effect, this despite a slight increase in circulating testosterone.
Aromatase is the enzyme that catalyzes the conversion of androgens (androstenedione, testosterone) to estrogens. It also is found in certain areas of the brain in high concentration (often in conjunction with 5-alpha reductase), specifically in areas that are essential for the neuroendocrine control of gonadotropin secretion and sexual behavior. Androgens are well known to be essential to sexuality, but without the concomitant presence of estrogens they are essentially without effect. Studies have demonstrated that the abolition of estrogen formation through the use of aromatase inhibitors, or resulting from a congenital aromatase defect, greatly reduces sexual desire and function despite the presence of normal or high androgen levels.
East German Research
A group of East German scientists performed what is probably the most elaborate “practical” research on the psychological benefits of androgens. Their research did not center much on the prosexual effects of androgens, but rather on what they termed the “psychophysical” properties.
The psychophysiological capacity, as the researchers describe it, is the ability of an individual to handle stress (physical, mental, and emotional). This capacity is determined by one’s ability to activate appropriate centers in the central nervous system. Psychophysiological capacity can be evaluated by applying stressful stimuli and measuring shifts in the alpha-frequency of an encephalogram. Specifically, the researchers found that physical or psychic stresses lead to increases of approximately 4 to 6 Hertz compared to the starting value in individuals possessing the psychophysiological capacity to handle the particular stress. If the stress becomes excessive for an individual, the alpha frequency decreases after passing through the 4-6 Hertz optimum, and can then sink to levels below the original baseline.
At the time that this research was carried out, there was a substantial government sponsored research effort in the field of athletic performance enhancement, and as you may have guessed, the aforementioned research was carried out on sportsmen. The alpha wave increase in athletes is associated not just with the physical stress of training or competition, but with the mental effort associated with preparation and the events themselves. The psychophysical capacity of the athletes, as measured by encephalogram, is adversely affected by circumstances such as false preparation, fear, overstressing, and disturbing personal problems. As a result performance often suffers substantially. The East Germans believed that not only was it vital to avoid such pre-contest stressors, but they also believed they had to find ways to increase one’s psychophysiological capacity so as to increase the ability to handle these pre-contest stressors (not to mention to handle the stress at contest time itself).
Now keep in mind that the matter of this research is not just applicable to athletes, but also to any one with decreased psychophysiological capacity (i.e. elderly), or who have to handle large amounts of stress (i.e. college exam studiers).
The East German’s discovered that appropriate administration of androgenic hormones had a marked effect on the psychophysiological capacity. Substances that they are known to have studied and used for this purpose include mestanolone (methyl DHT), Oral-Turinabol (dehydrochloromethyltestosterone), testosterone, and androstenedione. Of particular significance are the compounds mestanolone and androstenedione. These two substances are known to have minimal anabolic properties on muscle mass, yet their ability to activate the stress handling capabilities of the CNS are equal to or greater than that of testosterone or other androgenic / anabolic steroids.
One example in the literature describes the oral administration daily of 10mg mestanolone to 54 individuals who had been undergoing long term stress. An alpha wave increase of up to 4 Hertz was observed, and this was associated with a great increase in performance on tasks requiring high physical output, mental concentration and physical coordination.
Although effective, oral administration of androgens was not the preferred technique of the East Germans. Instead they preferred the intra-nasal route.
Due to the proximity of the nasal passages to the base of the brain, the East Germans believed that absorption here maximized the passage of steroids through the blood brain barrier and into the cerebrospinal fluid where they are available to stimulate genomic and non-genomic CNS androgenic activity.
The intranasal route was also fast acting, which made it ideal for pre-contest usage. According to the East German data, after intra-nasal administration, levels of steroids in the blood maximize at 15 minutes and decline to baseline by 90 minutes. Levels in the CNS are probably elevated even sooner (seconds to minutes). Furthermore, with the usage of intranasal testosterone and androstenedione, the East Germans discovered that the ratio of urinary testosterone / epitestosterone were normalized within 24 hours, allowing them to pass post competition drug testing.
Prohormones for CNS Activation
So what significance does all this have to the average reader here? It has quite a bit of relevance because legal, over the counter, androgenic prohormones are actually “custom made” for harnessing the CNS powers of androgens. As was previously mentioned with the enzymes 5 alpha-reductase and aromatase, the enzymes that convert prohormones to active androgens (17 beta hydroxysteroid dehydrogenase and 3alpha(beta) dehydrogenase) are also heavily localized in the many of the same CNS centers. Therefore, administration of these prohormones, while not always substantially raising systemic (blood) levels of active androgens, can cause large increases in androgen activity in the key CNS centers. As a result, these prohormones can be considered “CNS targeted” versions of testosterone. They should be considered valuable products due to the fact that they enable one to achieve many of the psychophysiological and prosexual benefits of testosterone, while avoiding much of the systemic toxicity associated with long term exogenous testosterone usage. Prohormones also give one the ability to achieve powerful immediate effects by limiting usage prior to times of important physical, mental or sexual tasks. The final message therefore, is that prohormones can be used safely, and possess potential benefits for a wide variety of people, regardless of whether muscle building is a priority to them or not.
Carani C, et.al., “Role of Oestrogen in Male Sexual Behavior: Insights from the Natural Model of Aromatase Deficiency”, Clin Endocrinol 1999, 51(4): 517-24
Celotti F et.al., “The 5 alpha-reductase in the Brain: Molecular Aspects and Relation to Brain Function”, Front Neuroendocrinol 1992, 13(2): 163-215
Choate JV, et.al., “Immunocytochemical Localization of Androgen Receptors in Brains of Developing and Adult Male Rhesus Monkeys”, Endocrine 1998, 8(1): 51-60
Mattern C, Hacker R, “Method for Nasally Administering Aerosols of Therapeutic Agents to Enhance Penetration of the Blood Brain Barrier”, German Patent Application DE9300442A1
Mattern C, Hacker R, “Medicament for Influencing the Degree of Activation of the Central Nervous System”, German Patent Application DE9300473A1
McClellan KJ, et.al., “Finasteride: A Review of its Use in Male Pattern Hair Loss”. Drugs 1999, 57(1): 111-26
Mooradian AD, et.al. “Biological Actions of Androgens”, Endocr Rev 1987, 8(1): 1-28
Poisson M, et.al., “Steroid Receptors in the Central Nervous System. Implications in Neurology”, Rev Neurol 1984, 140(4): 233-248
Roselli CE, et.al., “The Distribution and Regulation of Aromatase Activity in the Central Nervous System”, Steroids 1987, 50(4-6): 495-508
Zumpe D, et.al., “Effects of the Non-Steroidal Aromatase Inhibitor, Fadrozole, on the Sexual Behavior of Male Cynomolgus Monkeys (Macaca Fascicuiaris)”, Horm Behav 1993, 27(2): 200-15