Low Testosterone in Aging Men: TRT for Andropause

Andropause (male menopause) seems to hit aging men around age 50, when their declining testosterone levels (“low T”) begin to affect their health.  Osteoporosis, sexual dysfunction, fatigue, gynecomastia (male breasts), and metabolic syndrome are some of the symptoms. [9]  Should they start hormone replacement?  This is a bigger decision than it is for women, because if a woman starts hormone replacement and doesn’t like it, she can just stop, and she returns to her previous state.  But testosterone replacement therapy (TRT) in men shuts down natural testicular function because the LH (luteinizing hormone) and FSH (follicle stimulating hormone) negative feedback loops from the pituitary are suppressed if testosterone is administered.  The body senses the exogenous testosterone, tells the pituitary that no more needs to be produced, LH and FSH drop, and natural testosterone production is shut down.  This is similar to taking any thyroid medication with T3 in it, which suppresses TSH and any natural thyroid production.  There are also potential side effects of TRT that one should be aware of before committing to this protocol: high estradiol, erythrocytosis or thick blood, fluid retention, benign prostatic hyperplasia, gynecomastia, and testicular atrophy or infertility, to name a few. [1]  Most of these can be controlled by lowering the testosterone dose and dosing more often than once a week, or by managing the estradiol levels.

Testosterone replacement therapy is difficult to stop once started, because it shuts down natural testicular function.  Therefore, it is imperative that the cause of low testosterone be determined before starting the protocol.  Tests should be performed to determine whether one is primary, meaning the testicles have stopped functioning, or secondary, meaning the testicles work, but the problem is a defect in the pituitary hormone signals to make LH and FSH.  If one is secondary, HCG (Human Chorionic Gonadotropin) or HMG (Human Menopausal Gonadotropin) are available as shots to stimulate the testicles to produce.  If one is primary, then the options are transdermal gels like Androgel or Testim, or shots like testosterone cypionate.  Some insurance companies cover the shots but not the gels, others cover both, still others cover neither.  Shots are much less expensive than gels.  Creams or gels can also be made by compounding pharmacies for far less than the cost of the name-brand gels.

Estrogen in men is a common side effect of testosterone replacement therapy because of the aromatization (conversion) of testosterone to estrogen.  Prescription aromatase inhibitor medications like Arimidex or Aromasin can help control estrogen levels.  It is often difficult to get the dosage correct, however, and sometimes estrogen is too high, then too low.  This can negatively affect one’s “wood.”  DIM is an OTC supplement that helps some keep their estrogen levels down.  It enhances the bad estrogen to good estrogen conversion pathway so the liver can flush it out.  Sometimes, if thyroid and liver health can be optimized, estrogen levels will normalize without medication.  This is because thyroid levels affect the liver, which is responsible for processing out all the hormones.  So if thyroid levels are low, liver function will be suboptimal, and estrogen can build up.

Low testosterone can be caused by other hormone deficiencies, diet, and drugs.  Sometimes, just bringing thyroid hormone levels up will raise testosterone.  In other cases, the elimination of soy products, which are estrogenic, has brought levels back up.  Statin drugs will also lower testosterone, because testosterone is made from cholesterol. [10]

Testosterone levels can also decrease from excessive exercise like long-distance running.  This is similar to the reduced hormone levels found in women long-distance runners, whose monthly periods stop.  [7]

Testosterone shots were initially given by doctors once a month, at 400 mg/shot.  That left men with testosterone levels that peaked way above the normal range (in roughly 2-3 days), then eventually dropped to below what the man probably produced on his own.  These men would feel great shortly after the shots, but horrible in the last couple of weeks before their next shot.  In addition, estrogen levels would skyrocket as the body tried to lower the excess testosterone.

Over time, they figured out that a lower dose more often, like 100 mg/week, resulted in more physiological levels, because testosterone levels did not rise and fall so drastically.  Some men administer their testosterone shots every three days.  Weekly shots are a good starting point, but symptoms such as low energy by day 7 suggest that shorter intervals (every 3-6 days) at lower doses might work even better.  Note that just like thyroid doses range from ½ grain – 5+ grains, testosterone shots can range from 25 mg to over 100 mg per shot.  It is all very individual, and one should work with a doctor and get frequent lab tests when starting out.  If thyroid levels are low, it will usually limit testosterone’s life in the body and one will have to dose more frequently.  This is because SHBG (sex hormone binding globulin) levels affect the life of testosterone, and low thyroid levels are one cause of low SHBG.  Insulin resistance or diabetes is another one.  It is imperative that thyroid levels be monitored along with testosterone levels when on TRT, because they are interrelated, with the replacement of one affecting the other. [2, 3, 4]  Most doctors will run a TSH test to check thyroid health, but unfortunately, TSH levels often do not reflect thyroid levels and one must ask for more specialized thyroid tests.  [see links below for thyroid testing]

Hereditary hemochromatosis (HH) is a genetic, inherited disease where the body loads too much iron. One does not “get” this condition from testosterone replacement therapy.  However, too much iron in the blood can damage organs, so periodic bloodletting is standard practice for anyone with hemochromatosis.  Over time, high iron levels can damage the testicles and cause hypogonadism (low testosterone).

Thick blood or erythrocytosis can result from testosterone replacement therapy; RBC (red blood cells), hematocrit, and hemoglobin become elevated.  This is not the same as having too much iron.  After starting TRT, patients should be monitored for this condition with a CBC or Complete Blood Count.  Donating blood is the standard treatment for either hereditary hemochromatosis or thick blood, but if done too often in someone without hemochromatosis (more than twice a year), may deplete stored iron levels (ferritin) and lead to iron deficiency. [5,6]  This can lead to other problems like anemia and fatigue and will lower thyroid function, since thyroid needs adequate ferritin to work.  Multiple enzymes have iron as a component, so multiple biochemical processes will be negatively affected if ferritin drops too low.

Testosterone, hydrocortisone, and thyroid are all known to affect RBC levels.  Any one of these components in excess can cause erythrocytosis or thick blood.  Lower the excessive hormone, and the condition improves.  If testosterone, cortisol, and thyroid levels are optimal (neither too high nor low), blood should return to normal and there would be no need to donate blood all the time.  Sometimes, just taking a smaller testosterone dose more often does the trick.  For example, a 100 mg shot given every 10 days is equivalent to a 50 mg shot given every 5 days.  But the smaller dose will create less of a spike in testosterone, creating a more physiological (natural) level, and possibly, no thick blood.

For some hypothyroid men, the amount of T3 in natural desiccated thyroid may be too much, and they might do better combining T4 (levothyroxine) with a lower dose of desiccated thyroid split throughout the day.  If they are taking T3-only to combat high reverse T3, this will raise both SHBG and estradiol to unnatural levels, and result in more imbalance.  High SHBG is correlated with osteoporosis and fracture risk in men. [8]  In one study, T3 doses of 50-75 mcg daily resulted in accelerated bone turnover that resulted in bone loss. [11]

Getting your thyroid tested

If you’d like to have your thyroid levels tested, please ask for these thyroid tests, and note where your levels are in the thyroid lab ranges compared to healthy people.  If you do not ask for these specific tests, your doctor will most likely just run a TSH test, which sadly, does not catch many cases of hypothyroidism. [TSH levels do not reflect thyroid levels]

  1. Ernani Luis Rhoden, and Abraham Morgentaler. Risks of Testosterone-Replacement Therapy and Recommendations for Monitoring.  N Engl J Med 2004;350:482-92.  http://www.drdach.com/uploads/testosterone_rhoden.pdf
  2. Wayne Meikle. The Interrelationships Between Thyroid Dysfunction and Hypogonadism in Men and Boys.  Thyroid. April 2004, 14(supplement 1): 17-25. Available from: http://www.liebertonline.com/doi/abs/10.1089/105072504323024552
  3. H. Cavaliere, N. Abelin and G. Medeiros-Neto. Serum levels of total testosterone and sex hormone binding globulin in hypothyroid patients and normal subjects treated with incremental doses of L-T4 or L-T3.  Journal of Andrology, Vol 9, Issue 3 215-219, 1988.   Available from: http://www.andrologyjournal.org/cgi/content/abstract/9/3/215
  4. Tahboub R, Arafah BM. Sex steroids and the thyroid.  Best Pract Res Clin Endocrinol Metab. 2009 Dec;23(6):769-80. http://www.ncbi.nlm.nih.gov/pubmed/19942152
  5. Vahid Yousefinejad, Nazila Darvishi, Masoumeh Arabzadeh, Masoumeh Soori, Mahtab Magsudlu, and Madjid Shafiayan. The evaluation of iron deficiency and anemia in male blood donors with other related factors.  Asian J Transfus Sci. 2010 July; 4(2): 123–127.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937289/
  6. Toby L. Simon, Philip J. Garry, Elizabeth M. Hooper. Iron Stores in Blood DonorsJournal of the AMA. 1981;245(20):2038-2043.  http://jama.ama-assn.org/content/245/20/2038.abstract
  7. Garry D. Wheeler, Stephen R. Wall, Angelo N. Belcastro, David C. Cumming. Reduced Serum Testosterone and Prolactin Levels in Male Distance Runners. AMA. 1984;252(4):514-516. http://jama.ama-assn.org/content/252/4/514.abstract
  8. Lormeau C, Soudan B, d’Herbomez M, Pigny P, Duquesnoy B, Cortet B. Sex hormone-binding globulin, estradiol, and bone turnover markers in male osteoporosis.  Bone. 2004 Jun;34(6):933-9. http://www.ncbi.nlm.nih.gov/pubmed/15193539
  9. Dohle, G. R., et al. “Guidelines on male hypogonadism.” Eur Ass Urol (2012). http://www.uroweb.org/gls/pockets/english/15%20Male%20Hypogonadism_LR.pdf
  10. Schooling, C. Mary, et al. “The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials.”BMC medicine 11.1 (2013): 1-9. http://link.springer.com/article/10.1186/1741-7015-11-57#page-1
  11. Smith, Steven R., et al. “The effects of triiodothyronine on bone metabolism in healthy ambulatory men.” Thyroid 13.4 (2003): 357-364. http://online.liebertpub.com/doi/abs/10.1089%2F105072503321669848