Human growth hormone (HGH, somatotropin) is a naturally occurring hormone that stimulates tissue growth in humans. Adequate levels of sex steroids are crucial for maintaining metabolic health. To improve energy levels, lean body mass and other aspects of health, HGH supplementation and steroid supplementation are ways to increase sex hormone levels and in turn improve metabolic condition and energy levels. However, it is not necessarily clear which method is more effective or safe. While both HGH and steroid supplementation are helpful for increasing sex steroid levels, promoting growth of lean muscle tissue, and improving energy levels, most of the science conducted thus far is focused on individuals with deficiencies. For purposes of human enhancement, there is evidence that using either strategy can help to improve cognition and energy in older adults. In younger adults, there is very little evidence. Neither HGH or sex steroid supplementation should be used liberally without consultation with a physician. In general, HGH has a better safety profile than sex steroid supplementation,
Human growth hormone carries several major effects. Increased HGH will stimulate adipose cells to break down in order to derive energy. HGH also stimulates hepatocytes to produce more glucose in order to increase energy levels. The liver releases insulin-like growth factor (IGF-1), which subsequently acts on muscle to increase cell hypertrophy. IGF-1 also increases uptake of amino acids from the blood, which is a process that is useful for cell growth. Other beneficial effects of IGF-1 include increased production of all immune cells, as well as increased synthesis of neurotransmitters such as acetylcholine.
This diagram outlines the major growth-promoting effects of HGH, and the ensuing negative feedback from high HGH levels.
Typically, growth hormone levels are highest in young age, and start declining sharply after puberty is finished. Although growth hormone levels decline in adulthood, sex steroid hormones remain within an adult range until the mid-50s in age.
Studies have shown that HGH therapy is effective for increasing lean body mass in adults. In a study in 21 adults adults over age 60, it was found that HGH supplementation was helpful in increasing lean body mass by 8.8%, a 1.6% increase in bone density, and a decrease in adipose tissue by 14.4% (P<0.05). Specifically, the lean body mass increased from an average of 53kg to 58kg while total weight stayed at the same level of 78kg.1
There are serious side effects for HGH. The most obvious one is acromegaly, which refers to the enlargement of limbs such as hands and feet. Furthermore, HGH excess can result in muscle or joint pain, edema, irritability, and anhedonia (loss of pleasure).2
Testosterone therapy can be an attractive option for adults wishing to experience muscle growth and improve athletic performance. While it makes sense that these may serve as efficacious enhancement options, there is very little scientific evidence that supports this usage claim in healthy humans. Nonetheless, with the existing scientific literature, we can draw some conjectures on which hormonal therapies may be best.
There are various strategies from a supplementation perspective. The main options used today are androstenedione, Dehydroepiandrosterone (DHEA), and direct testosterone supplementation.3
Androstenedione is one hormonal supplement that serves as a precursor to testosterone and estradiol. For purposes of increasing muscle mass and strength, there is not enough rigorous research to confirm that androstenedione supplementation can lead to consistently raised levels of testosterone. For example, one study showed that a 5-day trial of 100mg/day of oral androstenedione supplementation did not increase plasma testosterone levels, but rather raised plasma estradiol levels.4A multitude of other studies also showed that estradiol levels increase with androstenedione supplementation.5,6
Another study showed that androstenedione supplementation for a 4-week period can lead to increased testosterone levels in people ranging in age from 30 to 50. In healthy 30 year olds, androstenedione therapy can help elevate testosterone levels from 70 pmol/L up to 100 pmol/L once individuals are 4 weeks into the therapy (P<0.05).
Testosterone is a sex hormone that is important for development of reproductive tissues, in the growth and maintenance of skeletal muscle tissue, and in maintaining high energy levels. One very prominent study involving testosterone supplementation in healthy men was performed in a cohort of 43 healthy men aged 19 to 40. In this study, one group received 600 mg of testosterone intramuscularly, once per week, for a period of 10 weeks. The other group received placebo injections over this period. Body weight, muscle size, mood and endocrine responses were measured throughout the treatment period. It was found that there were no significant differences in mood between the groups. However, the group getting testosterone therapy had about a 20% improvement in weightlifting (squat) one-rep maximum (maximum amount of weight lifted for one repetition). This is a good improvement, however, the placebo individuals that weight trained aggressively had the same 20% improvement. Considering muscle size, it was found that the testosterone group exhibited significantly greater muscle size (as measured by cross-sectional arm area) compared to the placebo group, regardless of whether or not the individuals exercised. Taken together, it appears that functional strength does not differ whether or not the individual takes testosterone, but muscle size can be significantly increased from testosterone supplementation. This study did not highlight any adverse effects from its patients, although it is important to consider them in future studies.7
Estrogen has been used in medicine as a therapy for women to treat postmenopausal symptoms, as well as treatment for osteoporosis (decreased bone density). For the purposes of human enhancement, it has been shown that estrogen may have stress mitigating effects. One study showed that estrogen administration can decrease molecular responses to mental stress in perimenopausal women. In this particular study 7 perimenopausal women took an estrogen supplementation (2mg/day) for a period of 8 weeks while 5 women took a placebo. The women took a basic math and arithmetic test, which serves as a stressor. Blood pressure, ACTH, epinephrine and norepinephrine levels were measured before and after the stressor. It was found that the women taking estrogen exhibited significantly smaller fluctuations in all of these measures as compared to the placebo group (P<0.05). This is promising as it indicates that estrogen may be able to attenuate the stress response. As increases in blood pressure and cortisol may lead to other complications down the line, it is helpful to keep those measures under control.8
In men, it is generally known that sex steroid loss (of both testosterone and estrogen) occurs in older age. Sex steroid loss usually leads to decreases in cognitive function. However, estrogen supplementation may help to improve cognitive state. One interesting study involved two groups of 18 patients, one of which were recovering from prostate cancer and the other of which were normal individuals. The group with prostate cancer received estrogen therapy in the form of an estradiol patch (0.6 mg/24 hours) every 7 days. Cognitive testing was done at baseline and at 4 weeks after the therapy. It was found that this group of patients exhibited significant improvements in performance on the Item Recall Test (30% more items recalled, P<0.01) and the Delayed Paragraph Recall test (35% more paragraphs recalled, P<0.01), two cognitive tests which are used to assess cognitive function in people with cognitive decline. However, there were no significant improvements in mood over the intervention period.9
With any of the aforementioned enhancement options, you have to be careful about excess levels of sex hormones. Yes, it is true that we define normal ranges of testosterone and estrogen based on the distribution of adults in the world. It is true that one can possess sex hormone levels in the upper tails or lower tails of the distribution and still live normally. However, a plethora of research out there consistently shows that people that reach certain levels of sex hormones are at increased rates of experiencing unwanted complications. Note that just because you have higher levels than others does not automatically mean you will experience these; but the statistics are there.
It is important to note that elevated estradiol levels can lead to a multitude of adverse effects. For example, androstenedione can lead to a two-fold increase in stroke risk (P= 0.03, n = 2525 patients)10, and increased rates of cardiovascular disease.11Furthermore, elevated estradiol is a risk factor for prostate cancer in males.12
We do not promote active supplementation with HGH or sex steroids for normal humans. In medicine, the usage of these therapies is currently reserved to people with medical deficiencies in growth hormone and sex steroid levels. While there is obviously widespread pedestrian usage of these among athletes, bodybuilders or anybody hoping to augment their potential, there are major long-term side effects from elevated sex steroid levels. If one was self-experimenting had to choose, mild HGH supplementation has a better safety profile. For purposes of human enhancement, we agree that this is an area that should be studied more, as there are great benefits to be attained from an HGH or steroid supplementation regimen that maintains a strong safety profile.
Rudman, D., Feller, A. G., Nagraj, H. S., Gergans, G. A., Lalitha, P. Y., Goldberg, A. F., ... & Mattson, D. E. (1990). Effects of human growth hormone in men over 60 years old. New England Journal of Medicine, 323(1), 1-6.
Rasmussen, B. B., Volpi, E., Gore, D. C., & Wolfe, R. R. (2000). Androstenedione Does Not Stimulate Muscle Protein Anabolism in Young Healthy Men 1. The Journal of Clinical Endocrinology & Metabolism, 85(1), 55-59.
King, D. S., Sharp, R. L., Vukovich, M. D., Brown, G. A., Reifenrath, T. A., Uhl, N. L., & Parsons, K. A. (1999). Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: a randomized controlled trial. Jama, 281(21), 2020-2028.
Bhasin, S., Storer, T. W., Berman, N., Callegari, C., Clevenger, B., Phillips, J., ... & Casaburi, R. (1996). The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. New England Journal of Medicine, 335(1), 1-7.
Komesaroff, P. A., Esler, M. D., & Sudhir, K. (1999). Estrogen Supplementation Attenuates Glucocorticoid and Catecholamine Responses to Mental Stress in Perimenopausal Women 1. The Journal of Clinical Endocrinology & Metabolism, 84(2), 606-610.
Beer, T. M., Bland, L. B., Bussiere, J. R., Neiss, M. B., Wersinger, E. M., Garzotto, M., ... & Janowsky, J. S. (2006). Testosterone loss and estradiol administration modify memory in men. The Journal of urology, 175(1), 130-135.
Lemaitre, R. N., Heckbert, S. R., Psaty, B. M., Smith, N. L., Kaplan, R. C., & Longstreth, W. T. (2002). Hormone replacement therapy and associated risk of stroke in postmenopausal women. Archives of internal medicine, 162(17), 1954-1960.
Horvath, L. G., Henshall, S. M., Lee, C. S., Head, D. R., Quinn, D. I., Makela, S., ... & Kooner, R. (2001). Frequent loss of estrogen receptor-β expression in prostate cancer. Cancer Research, 61(14), 5331-5335.
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