This series has been a long time coming as my time gets limited and other interests drive my focus elsewhere but TRT is still one of the things I most enjoy doing. The idea of this blog is to give a more medically based opinion on the 3 commonest injectables used in the UK; my experience with it and my patients’ experience with it including labs.
Firstly, I’d like to touch upon the fact that this blog is not referring to testosterone cycles- what you normally see in forums- that focus more on body building. The focus is on sub-optimal testosterone levels being brought back up to optimal levels.
The 3 commonest injectables that I use at my practice and their various quirks are summarised below:
commonest due to price.
Comes in ampoule only. If you are getting it online in a vial, its not from a UK pharmacy.
Claims to be sustained release- hence called susta-non due to having 4 different esters (or carrier molecules). Each ester releases the testosterone at a different time and hence you get a more staggered release pattern where the peaks and troughs are more stable.
Single 1ml shot lasts 2.5 to 3 weeks. It can be given in divided doses.
Main disadvantage- carrier oil is peanut oil and benzyl alcohol. This is becoming a problem I’m seeing more and more of as its giving rise to side effects which I don’t get with other injectables. Most people with mild intolerances generally don’t even know they cannot handle peanut oil. When given in such large doses (1ml into the muscle), it can cause pain and local inflammation that lasts much longer than expected. As part of my practice is gut dysbiosis where I see a lot of food intolerances, I recognised this very early on. If this is your experience too, try changing to the other injectables or use creams.
The average response I get when I ask about peanuts is that my patients love it! Do keep an open mind about intolerances- just because you love it does not mean that you can handle it. Look out for other symptoms of intolerances like joint pains, rashes, headaches, flu-like symptoms etc. You may get none, or all of them.
Testosterone Enantate 250mg
This is the most similar to Cypionate that many people read about in forums. Cypionate is available in the US and some other countries but not in the UK. Its what I would put my patients on who need continuity of care from the US.
Its quite a bit more expensive that sustanon- stupidly more in fact. I don’t know why!
Comes in ampoule only. If you are getting it online in a vial, its not from a UK pharmacy. The ones in vials are considerably cheaper- according to google and from what some of my patients tell me- but we practitioners will never advocate it. Its just not worth it to me.
Is given in the same way as Sustanon- either single shot that last 2-3 weeks or in divided doses.
Carrier oil here is castor oil which is less allergenic (apparently) and benzyl benzoate.
I personally have never had a complaint with this so suspect that it probably is less allergenic.
If the price point of this and sustanon were the same, I would prefer using this.
Nebido 250mg (4ml)
This can hurt but its usually due to the volume of product injected into a small area. I occasionally inject it either in both buttock cheeks especially in very slim patients, or change directions still with the same entry point to spread things out a little.
This comes in a vial.
Carrier oil here is refined castor oil which is less allergenic (apparently) and benzyl benzoate.
I’m not a huge fan of Nebido but it has its place. I personally prefer it for patients who have completed their family (for potential fertility implications), travel a lot, have compliance issues or similar reasons.
This always suppresses your pituitary hormones which means that the negative feedback generated will block your own production of testosterone.
On a practical level, a lot of people don’t mind it and are happy to put up with some testicular shrinkage- as long as everything is being monitored regularly.
Others freak out a little when their pituitary levels of LH comes back as close to nonexistent. They can either opt for a different option or start on a HCG protocol (Human Chorionic Gonadotropin) to stimulate their own production of testosterone alongside testosterone. Its a protocol used a lot in the US and quite many of my American patients request the same continuity of care as it works well for them.
There are also a small number who really feel the peak- not in a good way. Optimal levels of testosterone usually makes you calmer and less anxious but too much or too little can give rise to similar symptoms paradoxically when it comes to moods and aggression.
Bioidentical topical creams from Compounding Pharmacies- I use these a lot and my patients love them (mostly). They are much easier to use compared to the gels available on the NHS (messy, too large a volume and sometimes does not give the blood picture expected which may point to user inconsistency in application).
My topicals come in 3 forms- creams, gels or liposomal gel. I have so far only ever ordered the liposomal gel as its absorbability is far superior at no extra cost.
As these are bespoke, there is a period of trial and error until you find the right dose after which, we simply make the cream in said dose for each patient.
Its more physiological with everyday application and so mimics the body’s own production more closely. This also translate into less pituitary suppression.
Disadvantage- some people perceive creams to be less effective (not true). Some don’t like having to apply a cream everyday.
Transdermal Implants- not a commonly available option and I do not have much experience in it for testosterone. This is something I’m hoping to explore as I believe that there is a place for it seeing as it has a 4-5 month life cycle. My experience in implants is in contraceptive implants which I did not like. Similar to Nebido, my personal feeling is that in order to achieve such longevity, it needs to be quite powerful which can give rise to side effects initially. However, do watch this space as I’m hoping to explore this further and may find myself changing my mind about it.
I hope that this article will help you gain an idea of what is available legally via a pharmacy in this country and to be able to tell the difference between what may or may not suit you. Or why you may be reacting to something others don’t have a problem with. As with most things medical, its not quite that simple but getting the right balance is possible and certainly achievable.
Araujo, Andre B et al. “Clinical review: Endogenous testosterone and mortality in men: a systematic review and meta-analysis.” The Journal of clinical endocrinology and metabolism vol. 96,10 (2011): 3007-19. doi:10.1210/jc.2011-1137
Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, Chen X, Yarasheski KE, Magliano L, Dzekov C, et al Testosterone dose-response relationships in healthy young men. American Journal of Physiology: Endocrinology and Metabolism 2001. 281 E1172–E1181. (10.1152/ajpendo.2001.281.6.E1172)
Borst, Stephen E et al. “Cognitive effects of testosterone and finasteride administration in older hypogonadal men.” Clinical interventions in aging vol. 9 1327-33. 12 Aug. 2014, doi:10.2147/CIA.S61760
Cherrier MM, Craft S, Matsumoto AH. Cognitive changes associated with supplementation of testosterone or dihydrotestosterone in mildly hypogonadal men: a preliminary report. Journal of Andrology. 2003;24(4):568–576.
Corona, Giovanni, Giulia Rastrelli, Matteo Monami, André Guay, Jaques Buvat, Alessandra Sforza, Gianni Forti, Edoardo Mannucci, and Mario Maggi. "Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study". European Journal of Endocrinology 165.5: 687-701. < https://doi.org/10.1530/EJE-11-0447>. Web. 8 Aug. 2019.
Elisabeth Hak A., Jacqueline C. M. Witteman, Frank H. de Jong, Mirjam I. Geerlings, Albert Hofman, Huibert A. P. Pols, Low Levels of Endogenous Androgens Increase the Risk of Atherosclerosis in Elderly Men: The Rotterdam Study, The Journal of Clinical Endocrinology & Metabolism, Volume 87, Issue 8, 1 August 2002, Pages 3632–3639, https://doi.org/10.1210/jcem.87.8.8762
Emmelot-Vonk MH, Verhaar HJJ, Nakhai Pour HR, et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. The Journal of the American Medical Association. 2008;299(1):39–52.
Fletcher, Jenna and Daniel Murrell MD. "What are the symptoms of low testosterone?." Medicalnewstoday.com. Medical News Today, 1 Aug 2018. Web. 1 Jun 2019. <https://www.medicalnewstoday.com/articles/322647.php>.
Ghelani BPharm, MRPharmS, Rita. "Sustanon 250 injection (testosterone): a treatment to boost low testosterone levels." Netdoctor.co.uk. Netdoctor, 22 Jul 2019. Web. 1 Aug 2019. <https://www.netdoctor.co.uk/medicines/a7593/sustanon-injection-testosterone/>.
Giorgi, A, RP Weatherby and PW Murphy. "Muscular strength, body composition and health responses to the use of testosterone enanthate: a double blind study." Journal of Science and Medicine in Sport. 2.4 (1999): 341-55.
Haring, Henry Völzke, Antje Steveling, Alexander Krebs, Stephan B. Felix, Christof Schöfl, Marcus Dörr, Matthias Nauck, Henri Wallaschofski, Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20–79, European Heart Journal, Volume 31, Issue 12, June 2010, Pages 1494–1501, https://doi.org/10.1093/eurheartj/ehq009
Islam PhD, Rakibul, Robin Bell MBBS and Sally Green PhD. "Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data.." The Lancet Diabetes and Endocrinology. (2019): Web.<https://doi.org/10.1016/S2213-8587(19)30189-5>.
Jones, T. H., et al. “Testosterone Replacement in Hypogonadal Men With Type 2 Diabetes and/or Metabolic Syndrome (the TIMES2 Study).” Diabetes Care, vol. 34, no. 4, 2011, pp. 828–837., doi:10.2337/dc10-1233.
Khaw, Kay-Tee, et al. “Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men.” Circulation, vol. 116, no. 23, 2007, pp. 2694–2701., doi:10.1161/circulationaha.107.719005.
Kyriazis, Ioannis Tzanakis, Kostas Stylianou, Irene katsipi, Demitrios Moisiadis, Antonia Papadaki, Vasiliki Mavroeidi, Stella Kagia, Nikolaos Karkavitsas, Eugene Daphnis, Low serum testosterone, arterial stiffness and mortality in male haemodialysis patients, Nephrology Dialysis Transplantation, Volume 26, Issue 9, September 2011, Pages 2971–2977, https://doi.org/10.1093/ndt/gfq847
Lehtonen, Risto Huupponen, Jaakko Tuomilehto, Sirkku Lavonius, Seija Arve, Hannu Isoaho, Ilpo Huhtaniemi, Reijo Tilvis, Serum testosterone but not leptin predicts mortality in elderly men, Age and Ageing, Volume 37, Issue 4, July 2008, Pages 461–464, https://doi.org/10.1093/ageing/afn048
Maggio, Marcello et al. “Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging in the Chianti Area (InCHIANTI) study.” Archives of internal medicine vol. 167,20 (2007): 2249-54. doi:10.1001/archinte.167.20.2249
Mathur A, Malkin C, Saeed B, Muthusamy R, Hugh Jones T, Channer K. Long-term benefits of testosterone replacement therapy on angina threshold and atheroma in men. European Journal of Endocrinology. 2009;161(3):443–449.
Middleton, T., L. Turner, C. Fennell, S. Savkovic, V. Jayadev, A J Conway, and D J Handelsman. "Complications of injectable testosterone undecanoate in routine clinical practice". European Journal of Endocrinology 172.5: 511-517. < https://doi.org/10.1530/EJE-14-0891>. Web. 6 Aug. 2019.
Molly M. Shores, Nicholas L. Smith, Christopher W. Forsberg, Bradley D. Anawalt, Alvin M. Matsumoto, Testosterone Treatment and Mortality in Men with Low Testosterone Levels, The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 6, 1 June 2012, Pages 2050–2058, https://doi.org/10.1210/jc.2011-2591
Muraleedharan, Vakkat, Hazel Marsh, Dheeraj Kapoor, Kevin S Channer, and T Hugh Jones. "Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes". European Journal of Endocrinology 169.6: 725-733. <https://doi.org/10.1530/EJE-13-0321>. Web. 8 Aug. 2019.
Ng Tang Fui, Mark et al. “Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial.” BMC medicine vol. 14,1 153. 7 Oct. 2016, doi:10.1186/s12916-016-0700-9
Sartorius, Gideon et al. “Factors influencing time course of pain after depot oil intramuscular injection of testosterone undecanoate.” Asian journal of andrology vol. 12,2 (2010): 227-33. doi:10.1038/aja.2010.1
Seidman SN, Spatz E, Rizzo C, Roose SP. Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial. Journal of Clinical Psychiatry. 2001;62(6):406–412.
Selvin, E., et al. “Androgens and Diabetes in Men: Results from the Third National Health and Nutrition Examination Survey (NHANES III).” Diabetes Care, vol. 30, no. 2, 2007, pp. 234–238., doi:10.2337/dc06-1579.
Singh, Rajan. "Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors.." Endocrinology. January.147 (2006): 141-54.
Surampudi, Prasanth N et al. “Hypogonadism in the aging male diagnosis, potential benefits, and risks of testosterone replacement therapy.” International journal of endocrinology vol. 2012 (2012): 625434. doi:10.1155/2012/625434
Van der Meij, L, A Demetriou, M Tulin and I Mendez. "Hormones in speed-dating: The role of testosterone and cortisol in attraction.." Elsevier Hormonal Behaviour. (2019): Web.<https://www.ncbi.nlm.nih.gov/pubmed/31348926>.
Vlachopoulos, Nikolaos Ioakeimidis, Dimitrios Terentes-Printzios, Konstantinos Aznaouridis, Konstantinos Rokkas, Athanassios Aggelis, Alexandros Synodinos, George Lazaros, Christodoulos Stefanadis, Plasma Total Testosterone and Incident Cardiovascular Events in Hypertensive Patients, American Journal of Hypertension, Volume 26, Issue 3, March 2013, Pages 373–381, https://doi.org/10.1093/ajh/hps056
Wang C, Alexander G, Berman N, et al. Testosterone replacement therapy improves mood in hypogonadal men—a clinical research center study. The Journal of Clinical Endocrinology & Metabolism. 1996;81(10):3578–3583.
Wang C, Swerdloff RS, Iranmanesh A, et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. The Journal of Clinical Endocrinology & Metabolism. 2000;85(8):2839–2853.
Wehr, Elisabeth, et al. “Low Free Testosterone Is Associated with Heart Failure Mortality in Older Men Referred for Coronary Angiography.” European Journal of Heart Failure, vol. 13, no. 5, 2011, pp. 482–488., doi:10.1093/eurjhf/hfr007.
Weiss, Rita V., Hohl, Alexandre, Athayde, Amanda, Pardini, Dolores, Gomes, Larissa, Oliveira, Monica de, Meirelles, Ricardo, Clapauch, Ruth, & Spritzer, Poli Mara. (2019). Testosterone therapy for women with low sexual desire: a position statement from the Brazilian Society of Endocrinology and Metabolism. Archives of Endocrinology and Metabolism, 63(3), 190-198. Epub July 18, 2019.https://dx.doi.org/10.20945/2359-3997000000152
Wieselman, Brie. "Adrenal Fatigue Part 4: The “Cortisol Steal”—or, How Increased Stress Creates Female Hormone Imbalance." Briewieselman.com. 1 Jan 2018. Web. 1 Aug 2019. <https://briewieselman.com/adrenal-fatigue-part-4-the-cortisol-steal-or-how-increased-stress-creates-female-hormone-imbalance/>.
Zoë Hyde, Paul E. Norman, Leon Flicker, Graeme J. Hankey, Osvaldo P. Almeida, Kieran A. McCaul, S. A. Paul Chubb, Bu B. Yeap, Low Free Testosterone Predicts Mortality from Cardiovascular Disease But Not Other Causes: The Health in Men Study, The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 1, 1 January 2012, Pages 179–189, https://doi.org/10.1210/jc.2011-1617