Hormones play a core role in male fertility, and they affect sperm production, mood, libido and a multitude of general health issues. Testosterone is the primary male sex hormone, and infertile men are much more likely to have abnormally low levels of:
- Luteinising hormone (LH)
- Adrenaline and noradrenaline
However, there are two hormones from the anterior pituitary that are usually elevated in infertile men:
- Follicle-stimulating hormone (FSH)
Hormones and male fertility
Sex hormones work in sequence in the hypothalamus-pituitary-testes axis, with high levels of one hormone regulating the levels of the others via a “negative feedback system”.
- The hypothalamus releases gonadotropin-releasing hormone (GnRH), which stimulates the anterior pituitary.
- The anterior pituitary releases two hormones: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and they act directly on the testes.
- FSH and LH bind to receptors in the testes and regulate their function by promoting the production of sex hormones (mainly testosterone) and sperm. FSH, LH and testosterone are all essential for healthy sperm.
Actions of the hormones
- LH stimulates testosterone production in the Leydig cells of the testes.
- FSH stimulates the growth of testicles and encourages the Sertoli cells to make an androgen-binding protein that increases testosterone concentrations near to sperm, which is essential for normal spermatogenesis.
- However, high FSH levels are linked to damage in the seminiferous tubules, abnormal testicular function and low fertility:
- Causes of high FSH include damage to the testicles (from radiation, trauma, or alcohol), genetic conditions, ageing, hormonal disorders, some medications (pain meds or steroids), HIV/AIDS, Type 2 diabetes or pituitary tumours.
- Both low and high FSH levels are linked to hypogonadism, and men will experience erectile dysfunction, low libido, little energy and infertility.
- Prolactin excess is a well-known cause of male and female infertility. Prolactin levels are controlled by dopamine secreted from the hypothalamus, and hyperprolactinemia is either caused by interference with dopamine action or due to a pituitary adenoma.
- Dopamine is a “pleasure” hormone with other vital roles in male sexuality, as dopamine levels affect libido, prolactin levels and male sexual function.
- Low testosterone levels with raised FSH levels cause damage to Leydig cells and the seminiferous tubules of the testes.
Testosterone is the most important androgen for sperm production, male fertility, libido, muscle mass and bone health. Testosterone levels tend to fall by 1% each year from 30 and by 1-2% after 40. [ii] By the age of 60, a man’s testosterone levels are typically only 40-50% of his youth levels, with chronic stress and negative lifestyle choices such as diet, exercise, and poor sleep patterns accelerating testosterone decline. The fall in testosterone varies considerably due to a combination of:
- Lower GnRH levels
- Changes in the androgenic negative feedback system
- Less responsive testicular tissue [iii]
Higher sex hormone binding globulin (SHBG) and lower albumin* levels also contribute to lower Free Testosterone levels. The combination of these factors makes more testosterone bind to SHBG and reduces free (bioavailable) testosterone. . [iv]
*Albumin is a blood protein that carries hormones, vitamins, and enzymes. It also helps prevent fluid leaking from the blood vessels, and low levels are associated with various conditions (liver, kidney, digestive, burns, thyroid) and ascites.
Low Testosterone Conditions
There are many benefits to maintaining healthy testosterone levels:
- Greater muscle mass.
- Less body fat.
- More psychological vigour and resilience.
- Better general well-being.
While a reduction in testosterone is associated with “Androgen Deficiency” (AD) which can occur at any age, and “Late-onset hypogonadism” (LOH) or “Ageing Male Syndrome” (AMS) that affects men over 40. All low androgen conditions are 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]
- 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 the risk of mortality in men five-fold, even after controlling for age, BMI, current smoking, and general health.
The significant semen-related factors of low serum testosterone are:
- Low sperm count
- Poor sperm motility
- Abnormal sperm morphology
- Small sample sizes
Drugs that reduce testosterone
- Statins because androgens (and other sex hormones) require cholesterol for their formation; a reduction in cholesterol will affect the ability to create sex hormones.
- Metformin for raised blood sugar levels in men with Type II diabetes
- Opioids, especially when taken long-term for pain
- Anti-hypertensives (Inderal, Clonidine, Reserpine, Lasix) for high blood pressure
- Antidepressants (SSRI’s, tricyclics, MAOi’s) for anxiety and depression
- Tranquillizers (Haldol, Thorazine, Zyprexa, Seroque)
- Anticholinergics (Benadryl, Donnatal, Pro-Banthine, Cogentin) used for spasm or incontinence
- Beta-blockers decrease testosterone and impede arousal by interfering with nerve impulses
- H2-receptor antagonists, (Tagamet, Zantac) for gastrointestinal disorders (such as gastroesophageal reflux and peptic ulcers)
[i] By Testosterona-ciclo.png: Acraciaderivative work: Boghog2 – Testosterona-ciclo.png, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11186183
[ii] Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab 2002;87:589–98.
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[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.
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[xiii] 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.
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