At first glance, the actions and signaling of male reproductive hormones seem MUCH less complex compared to the female reproductive hormone cycle. Yet despite this, it's the controversial USE of exogenous hormones, particularly in the area of athletic performance enhancement and body composition changes, that seems to muddy the waters regarding our general understanding of what these hormones actually do. ['Exogenous' meaning additional administration, or outside of your normal/natural production; for this topic, we are looking at exogenous hormones commonly referred to in mainstream media as 'anabolic steroids'] Despite the continued use of anabolic androgenic steroids (AAS) in the sport and fitness world, there still seem to be misconceptions or misled assumptions as to what they actually do, and why they are so controversial.
First, let's look at what these hormones actually are and what they do...
Similar to the hormonal signaling that begins in the brain for the female reproductive hormone cycle, the initiation of hormone production in males also begins in the brain, specifically the hypothalamus. During puberty, the hypothalamus (in the brain) secretes the hormonal factor GnRH that triggers the pituitary gland (also in the brain) to secrete FSH. This secretion of FSH also upregulates LH receptors so that the pituitary gland can then also secrete LH. In males, FSH stimulates sperm cell production in specialized cells of the testes, while LH stimulates the production of testosterone in the testes. Unlike the fluctuating hormones that occur with females, males have a pretty stable pulsatile output of GnRH from the hypothalamus, and thus relatively stable sperm production and testosterone secretion in the testes throughout their adult life, however with a natural decline with aging.**The exception occurs in hypogonadal men where there may be decreased pulsing of GnRH from the hypothalamus, even as a younger adult, leading to less FSH and LH from the pituitary gland, and thus subsequent decreases in natural production of testosterone.
Declines in circulating testosterone are also seen in cases of overweight and obesity, regardless of age. Study findings show that overweight and obesity are most notably associated with declining testosterone levels in men due to insulin resistance-associated reductions in sex hormone binding globulin and suppression of the hypothalamus-pituitary-testes axis that was noted above. (Kumagai, et al. 2017) Even more, obesity is associated with declining testosterone levels, AND low testosterone is associated with increasing weight and fat gain, creating a self-perpetuating cycle. (Kumagai, et al. 2017) In addition to increased fat gain, low testosterone is also associated with insulin resistance, endothelial dysfunction (like circulatory/cardiovascular complications), cognitive dysfunction, and low bone mineral density. (Kumagai, et al. 2017) Study findings show that lifestyle modifications like physical activity and diet are associated with increasing testosterone concentrations in overweight and obese men, with an emphasis placed on the role that an increase of physical activity (and increased INTENSITY of this physical activity) has versus just dietary caloric restriction alone. (Kumagai, et al. 2017) In this study, the more vigorous the physical activity, the greater the increase in testosterone in a sample of overweight/obese men that had low testosterone concentrations at baseline. (Kumagai, et al. 2017) *This study was just based on aerobic activity using walking/jogging, for a 12 week exercise intervention including up to 90 min/day for 1-3 days/week for the 12 weeks.
Further study findings show that resistance training protocols can increase natural production of testosterone, as well as growth hormone and IGF-1, all of which are important hormones in stimulating muscle growth. (Fink, et al. 2017) It is theorized that resistance training elevates these post-exercise anabolic hormones binding to their receptors possibly leading to enhanced protein synthesis with decreased protein breakdown, satellite cell activation, and possibly increasing intracellular calcium which would then play a role in more forceful muscle contractions and which could improve training intensity. (Fink, et al. 2017) In addition to testosterone, growth hormone (GH) is notably associated with anabolic processes where it is naturally secreted during sleep (within the first 90 minutes of nocturnal sleep) and signals the release of insulin-like growth factor (IGF-1). (Fink, et al. 2017) In this case, there are indirect effects on muscle cell growth from GH or IGF-1 as the uptake of nutrients into the cells can subsequently foster protein synthesis as well as glycogen and triglyceride synthesis. (Fink, et al. 2017)
But what exactly does testosterone DO?
The androgens (testosterone and estrogen) refers to the group of hormones responsible for sex characteristics and reproduction. Testosterone however has BOTH androgenic actions (male sex characteristics) AND anabolic actions (building up cells/tissues). Starting at puberty, testosterone and the testicular androgens:
Enhance protein synthesis in skeletal muscle leading to a more masculine body growth and physique (and subsequent sodium, potassium, and water retention)
Enhance bone formation and closure of the epiphyseal plates (and subsequent calcium retention)
Vocal chord development and voice deepening
Hair growth (facial, chest, pubic, general body surface), hair loss (forehead), growth of sebaceous glands in the skin (acne)
Sperm formation, reproductive organ growth, prostate gland growth, etc
Increased libido (central nervous system sexual activity)
And what about in females?
Both men and women produce BOTH testosterone and estrogen, but in different ratios where for example the female ovaries contribute 25% testosterone production with the other 75% coming from weaker adrenal androgens (specifically androstenedione and DHEA). (Huang and Basaria, 2017) During the follicular phase (first half of the female menstrual cycle) testosterone and androstenedione increase and peak prior to ovulation, but androstenedione continues to increase into the luteal phase (second half of the cycle) while testosterone does not increase further. (Huang and Basaria, 2017) There are reported physical performance benefits noted in female athletes with endogenous hyperandrogenism (naturally HIGH production of the androgens) where for example these women are biologically predisposed to produce comparatively higher concentrations of testosterone than the average ranges of testosterone concentrations seen in non-hyperandrogenic women. (Huang and Basaria, 2017) In this population, there are reported increases in lean muscle mass and these individuals were more likely to participate in sprint type events (or events that require strength, power, and speed). (Huang and Basaria, 2017) Interestingly, this population also has a higher risk and prevalence of PCOS (polycystic ovarian syndrome). (Huang and Basaria, 2017)
But when it comes to taking exogenous testosterone...
In many cases, the most widely utilized reason for taking exogenous testosterone (additional testosterone administration outside of what is normally produced in your own body) recreationally is likely due to its anabolic effects on muscle protein synthesis, cartilage, and other target tissues. (Hadley and Levine, 2009) It is noted that these anabolic effects (building up of cells/tissues) of testosterone may be directly attributed to:
1. Its ability to increase retention of dietary nitrogen (from dietary protein/amino acids). (Hadley and Levine, 2009) [Think of this as an enhanced ability to actually USE the protein you eat for building up cells/tissues.]
2. Study findings show that testosterone exerts insulin-like effects in muscle cells, of which are highly sensitive to insulin, specifically by up-regulating Glut4 receptors, increasing IGF-1, and increasing mTORC1 activation. (Antinozzi, et al. 2017) [Side note: insulin is known as an 'anabolic hormone' because it facilitates the transport of nutrient INTO the cells, and thus their USE or STORAGE, i.e. building. Without proper insulin signaling, nutrients stay in the blood, meaning they will NOT enter the cells, and therefore CANNOT be used or stored properly, i.e. CANNOT build.]
*Glut4 receptors in the skeletal muscle cells facilitate the entry of glucose into the cells, and are also upregulated by insulin binding to its receptor.
**IGF-1 is insulin-like growth factor which mediates cellular growth and is signaled in response to growth hormone (GH).
***mTORC1 is a signaling pathway that mediates cellular growth.
When insulin-like actions are increased and cellular growth pathways are stimulated, anabolism (the building up of cells/tissues) will likely take place. Notably, since testosterone increases IGF-1, which increases the mTORC1 pathway of muscle protein synthesis, it is suggested that LOW testosterone decreases IGF-1 and mTORC1 so there is MORE muscle wasting/less muscle protein production (in cases of low testosterone), to where anabolic steroid administration (nandrolone) was shown to reverse this muscle wasting in castrated mice. (White, et al. 2014) *Side note: the term 'steroid' simply refers to a hormone that is synthesized from cholesterol (NOT 'bad' or 'illegal' or any other connotation)
3. Additionally, it is theorized that androgens (sex-defining hormones) stimulate satellite cell formation and differentiation into myoblasts, which can then attach to already-present muscle fibers to comprise new muscle tissue. (Hadley and Levine, 2009) i.e. building up of muscle tissue
4. Finally, it is theorized that these anabolic actions of androgens on skeletal muscle can INHIBIT protein/muscle catabolism (LESS muscle/protein breakdown). (Hadley and Levine, 2009)
*Short answer: Yes, they work. But they do not simply 'make you strong' or 'make you big'. Instead, they increase the ABILITY to retain and ABILITY to build muscle mass; the hard work still needs to take place (resistance training, eating appropriately, etc). But by modulating and preserving muscle protein synthesis, they can indirectly ENHANCE RECOVERY in a way that a higher volume of training can take place without sacrificing muscle mass, and thus 'quicker gains' or comparatively faster results from training (compared to an athlete NOT using exogenous hormones).
How testosterone plays a role in sports...
Increased muscle protein synthesis, increased muscle fiber growth, and decreased muscle breakdown are all obviously favorable attributes to any athlete because:
Increased muscle fiber growth is associated with hypertrophy (increased size/muscle cell cross-sectional area) and overall building of an aesthetic physique (like in bodybuilding athletes).
Increasing and maintaining muscle fibers is important for athletes training at high volumes (regardless of sport) so that they can preserve their strength, speed, power, and even endurance, while training at high volumes.
In essence, this would equate to enhanced recovery (of muscle protein fibers) so that the athlete could get back to training quickly (or maintain a high volume of training) without sacrificing their muscle mass (and thus strength, speed, power, endurance, etc) in the process.
Okay, I see what the appeal is, so why not just let all athletes use these exogenous hormones?
Several reasons, including but not limited to:
Moral/ethical issues of training or competing in an altered state (NOT your natural-born state)
Accessibility is not universal and often times questionable
Undue health effects and serious negative consequences are only beginning to surface (we are JUST NOW finding out the magnitude of the health risks and it doesn't look good)
For example, it is theorized that testosterone administration could be associated with enhanced growth of prostate cancer, as well as increased red blood cell production which can thicken the blood and raise the risk of stroke, in addition to the other potential complications arising from water and sodium retention (increased risk for hypertension/high blood pressure), and altered feedback mechanisms. (Hadley and Levine, 2009) *With the 'altered feedback mechanisms', the circulating levels of testosterone in the blood send a signal (feedback) to the brain that there is enough testosterone already in the blood, so no need to continue that signal to make more (i.e decreased production of GnRH, FSH and LH, and then less natural testosterone production). With this decrease in natural production of testosterone, those testosterone-producing cells in the testes are now at an increased risk for undue growth or modulation (like tumor formation). **It begs the question as to whether we should be SURPRISED to hear of the extent of hormonal substance abuse in a certain highly functioning, young, healthy male athlete who was suddenly ridden with testicular cancer that metastasized to his brain. [Think about those circulating hormones in the blood, where they send their feedback/messages to, and how those cells are no longer producing the hormones they are SUPPOSED to be producing, thus increasing risk for abnormal cell functions.] In hindsight, those dramatic cancer diagnoses in an otherwise superhuman athlete should have been a dead-ringer red flag of exogenous (outside of his normal hormone production) hormonal supplementation.
What about adverse health effects in the short term?
Androgen-anabolic steroids (AAS) aim to utilize the anabolic effects (muscle building) of testosterone without the additional adrogenic effects (sex characteristics like hair growth, skin/acne, voice, emotions, etc). Regarding the anabolic effects of androgen-anabolic steroids (AAS), study findings have reported an observed increase in body weight of 2-5kg and strength gains of 5-20% from baseline in trials of short-term administration of these AAS drugs in athletes. (Hartgens and Kuipers, 2004) There were also some observed effects on erthropoeisis (increased red blood cell production) and hemoglobin concentrations (which produces a thicker consistency to the blood, making it harder to push through the vascular system, therefore leading to increased blood pressure and risk for occlusion of vessels and arteries). (Hartgens and Kuipers, 2004) Despite the increase in red blood cell production, there was NOT an effect on endurance capacity, which again may be due to the increased thickness of the blood (harder to push the blood through the vascular system). (Hartgens and Kuipers, 2004) Reported side effects by the athletes including increased sex drive, acne, aggression, and body hair. (Hartgens and Kuipers, 2004) Some of the adverse health effects include reduced natural production of testosterone and increased cardiovascular risk factors (from SHORT TERM USE= within 4 weeks of use) like increased blood pressure and decreased HDL cholesterol (the 'good' cholesterol), as well as increased risk for atherosclerosis from unfavorable blood lipid and lipoprotein concentrations, vasospasm, thrombosis, or direct injury to blood vessel walls. (Hartgens and Kuipers, 2004) **Take note: these side effects were noted after only 'short-term administration' of these AAS.
What about the long-term effects?
When it comes to the long-term health outcomes, there are study findings to suggest that in a population of male bodybuilders, 'regular users' of anabolic androgenic steroids had higher blood pressure and higher cardiac sympathetic modulation with lower parasympathetic modulation compared to non-using bodybuilders and sedentary controls. (Neto, et al. 2017) This translates to a REDUCED ability to keep resting heart rate low, AND an increased rise in heart rate upon exertion i.e. heart rate may be racing while at rest, AND it speeds up quickly as soon as you begin activity. The left ventricular wall of the heart was thicker in the users compared to the non-users and control group which is associated with an enlargement of those cardiac muscle fibers in response to an increased pressure in the aorta in order to push the blood out to the body (high blood pressure). (Neto, et al. 2017) In this study, 'users' of these AAS had been regularly using AAS for at least two years where the average use for this study population was 3.8 years (2-4 cycles per year) with a mean weekly dose of 646mg largely from nandrolone decanoate, testosterone propionate, stanozolol, and testosterone cypionate. (Neto, et al. 2017) *As mentioned above, a chronically elevated testosterone level (like 10x greater than normal concentrations) would feedback to the brain (telling the brain that there is plenty in circulation, so no need to produce any more) and therefore cease production of GnRH and further decrease production of FSH and LH. With this feedback response, those cells that would normally produce testosterone in response to these hormonal signals, would therefore cease their normal functions and atrophy (or are at an increased risk for abnormal cell functions). **This is why the cells of the testes can atrophy (decrease in size) in response to testosterone and AAS abuse.
But exercise increases testosterone naturally, so how do these compare?
To compare regular resistance training to the use of AAS: a single bout of resistance training (moderate intensity, high volume, short rest periods, with large muscle groups) can reportedly increase testosterone levels to about 650 ng/dL for about 60 minutes post-exercise. (Fink, et al. 2017) This is in comparison to an average/'low' dose of testosterone replacement therapy (like for aging men) of 200mg biweekly equating to sustained daily average of 815 ng/dL (and this is the "low dose" according to AAS users). (Fink, et al. 2017) While a healthy male may produce betwen 2-11mg testosterone/day, a survey of AAS users suggested that over 50% use more than 1000mg/week (or 10x the normal physiologic concentrations). (Fink, et al. 2017) It has been observed that in bodybuilding populations of AAS use, cycles of 4-12 weeks of supraphysiologic doses of testosterone consist of 250-3500 mg/week, or up to 40x greater than recommended dosages for hormone replacement therapy. (Saudan, et al. 2006)
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