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Treatments for Low Testosterone

Testosterone (T) is an “androgen”, one of the hormones that give men their “male” characteristics. Androgens are essential for developing the male reproductive organs (penis, prostate, seminal vesicles, vas deferens, and epididymis) when baby boys develop in the womb.

The body stops making sex hormones a few months after birth and restarts at puberty, and testosterone is the primary male hormone essential for sexual function and fertility.

Low testosterone (low T) is a significant cause of male infertility, but sperm production relies on more than one hormone, which makes it essential that each case is carefully assessed before a treatment option is chosen.

Androgens change how the body works by stimulating the androgen receptors (ARs) found in all male sex organs. Testosterone (T) and its derivative, dihydrotestosterone (DHT), which is 2.4x more potent than T, are the two most important androgens. The testes need high androgen levels to make the ARs stimulate testicular function and produce sperm.

However, about 1.7% of infertile men have AR gene mutations that prevent them from responding to testosterone. [i] (which is in addition to other causes of Androgen Insensitivity Syndrome).

There’s a natural variation in normal T levels, and in non-obese American and European men aged 19 to 39, they’re: [ii]

Percentile T level ng/dL
5th 303
50th (average) 531
95th 852

Testosterone levels naturally fall with age, and the average male T level in age groups are:

Age T level ng/dL
19-39 507
40-49

461

50-59 446
60+ 446

Although testosterone falls with age, it’s not the most significant factor affecting T levels in men wishing to become fathers. The falls in male T concentrations in the last 30 years far outweigh the age issue, and it may not be due to specific health or lifestyle trends. [iii] Exposure to man-made endocrine-disrupting chemicals (EDCs) in the womb and adulthood is changing male fertility. There are many benefits to maintaining healthy testosterone levels:

  • Greater muscle mass
  • Less body fat (especially abdominal fat)
  • More psychological vigour and resilience
  • Better general well-being

Men with testosterone deficiency have a variety of symptoms:

  • Low libido
  • Fatigue
  • Greater fat mass
  • Osteoporosis
  • Erectile dysfunction

 

Testosterone replacement therapy (TRT)

Testosterone replacement therapy (TRT) significantly increases the survival rates of hypogonadal men, [iv] which is crucial because testosterone deficiency is associated with a range of morbidities:

  • Major depressive disorder [v]
  • Type 2 diabetes [vi]
  • Obesity [vii]
  • Metabolic syndrome [viii]
  • Cardiovascular disease [ix]
  • Cognitive decline [x]

Low T also significantly reduces the quality of life and increases the risk of mortality in men: [xi] [xii]

  • Men with the lowest total testosterone levels are 40% more likely to die in 12 years than other men (after controlling for age, obesity, and lifestyle).
  • Severe “late-onset hypogonadism” (LOH) raises men’s mortality risk five-fold, even after controlling for age, BMI, current smoking, and general health.

However, TRT use is controversial because it’s associated with an increased risk of exacerbating pre-existing medical conditions, which is why TRT is contraindicated for men with:

  • Any existing prostate disease
  • Elevated hematocrit concentrations
  • High CVD risk
  • Obstructive sleep apnoea

The US FDA and the Endocrine Society of Australia only recommend TRT for cases of “classic” or irreversible Androgen Deficiency (AD) rather than “functional”, age, or comorbidity-related AD.

Androgen receptors (ARs) don’t distinguish between T made in the testes or given as a supplement, and healthy sperm production requires low levels of follicle-stimulating hormone (FSH) and luteinising hormone (LH). [xiii]

High testosterone levels suppress GnRH production from the hypothalamus and will ultimately inhibit LH/FSH production in the pituitary. Without FSH and LH involved in sperm production, men are infertile.

The 2013 European Association of Urology Guidelines on Male Infertility clearly state that:

“Testosterone suppresses pituitary production of LH and FSH; therefore, replacement therapy should not be given for infertility”. [xiv]

Despite this clear guidance, up to 25% of urologists have used T replacement therapies to treat male fertility, [xv] and many sources continue to recommend it as a fertility treatment. Straight-line thinking doesn’t work well in this situation.

 

Self-medication

Unsurprisingly, many men take T supplements to increase muscle mass and improve their fertility. Around 1.3% of men attending infertility clinics admit taking T to treat hypogonadism and infertility (88% had azoospermia). However, not all men admit to T use, so any men with LH below 0.06 IU/L should be asked about external T exposure.

Stopping T replacement therapy is the appropriate first step for these men wanting children:

  • 50% normalise their T levels within six months
  • 95%–98% normalise their T levels in 15–18 months
  • 65 to 94% recover the ability to make sperm. [xvi] [xvii]

Strategies that increase male testosterone production and concentrations and avoid the potential TRT risks are highly desirable and revolve around herbal options.

 

Herbal options for low male testosterone

Herbal products are increasingly popular due to several factors; they’re seen as effective, with a long history of traditional use and are relatively safe, with few records of serious side effects.

Sales have increased yearly for over a decade, and about US$8.8 billion of products were sold in 2018. Studies show some herbs are effective treatments for many male fertility conditions, even when they don’t raise testosterone. [xviii] Herbs can improve the function of the hypothalamus-pituitary-testes axis, immune health and elevate T levels. We have formulated the most compelling herbs in a unique blend. The herbs with the most robust research to support beneficial effects on sex hormones are:

Herb Testosterone Luteinizing hormone (LH) Follicle-stimulating hormone (FSH) Prolactin Adrenaline & noradrenaline SHBG

 

Trigonella foenum-graecum Improved Possible improvement Improved
Withania somnifera Improved Improved Improved Improved Improved
Tribulus terrestris Inconclusive No change
Mucuna pruriens Inconclusive Improved Improved

 

Improved Improved
Eurycoma longifolia Improved Improved

 

References

[i] Ferlin A, et al. Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations. Clin Endocrinol. 2006; 65: 606-610
[ii] Thomas G. Travison, et al, Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe, The Journal of Clinical Endocrinology & Metabolism, Volume 102, Issue 4, 1 April 2017, Pages 1161–1173, https://doi.org/10.1210/jc.2016-2935
[iii] Thomas G. Travison, et al.  A Population-Level Decline in Serum Testosterone Levels in American Men, The Journal of Clinical Endocrinology & Metabolism, Volume 92, Issue 1, January 2007, Pages 196–202, https://doi.org/10.1210/jc.2006-1375
[iv] Shores MM, Smith NL, Forsberg CW, Anawalt BD, Matsumoto AM. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab 2012;97(6):2050–8.
[v] Joshi D, van Schoor NM, de Ronde W, Schaap LA, Comijs HC, Beekman AT, Lips P. Low free testosterone levels are associated with prevalence and incidence of depressive symptoms in older men. Clin Endocrinol (Oxf) 2010;72(2):232–40.
[vi] Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and metaanalysis. JAMA 2006;295(11):1288–99.
[vii] Traish AM, Zitzmann M. The complex and multifactorial relationship between testosterone deficiency (TD), obesity and vascular disease. Rev Endocr Metab Disord 2015;16(3):249–68.
[viii] Antonio L, Wu FC, O’Neill TW, et al. EMAS Study Group. Associations between sex steroids and the development of metabolic syndrome: a longitudinal study in European men. J Clin Endocrinol Metab 2015;100:1396–404.
[ix] Corona G, Rastrelli G, Monami M, Guay A, Buvat J, Sforza A, Forti G, Mannucci E, Maggi M. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eur J Endocrinol 2011;165(5):687–701.
[x] Hsu B, Cumming RG, Waite LM, et al. Longitudinal relationships between reproductive hormones and cognitive decline in older men: the concord health and ageing in men project. J Clin Endocrinol Metab 2015;100:2223–30.
[xi] Maggi M, Schulman C, Quinton R, Langham S, Uhl-Hochgraeber K. The burden of testosterone deficiency syndrome in adult men: economic and quality-of-life impact. J Sex Med 2007;4(4 Pt 1):1056–69.
[xii] Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab 2008;93(1):68–75.
[xiii] By Artoria2e5 – Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=81460023
[xiv] Jungwirth A., et al. Guidelines on male infertility. EAU Publ. 2013; 35
[xv] Ko E.Y. et al. Empirical medical therapy for idiopathic male infertility: a survey of the American Urological Association. J Urol. 2012; 187: 973-978
[xvi] Samplaski M.K. et al. Testosterone use in the male infertility population: prescribing pattern and effects of semen and hormonal parameters. Fertil Steril. 2014; 101: 64-69
[xvii] Liu P.Y. et al. Hormonal male contraception summit group. Rate, extent, and modifiers of spermtogenic recovery after hormonal male contraception: an integrated analysis. Lancet. 2006; 367: 1412-1420
[xviii] Stephen J Smith, Adrian L Lopresti, Shaun Y M Teo, Timothy J Fairchild, Examining the Effects of Herbs on Testosterone Concentrations in Men: A Systematic Review, Advances in Nutrition, Volume 12, Issue 3, May 2021, Pages 744–765, https://doi.org/10.1093/advances/nmaa134