Ultimate Guide To Testosterone

Introduction

Testosterone levels are declining. It’s hard to avoid noticing. Headlines reporting the steady decline in men’s testosterone are found everywhere across the internet, along with the sharp rise in the number of supplements purported to boost this vital hormone. It might seem overblown, but it’s true that testosterone is critical for male health, and it’s certainly a subject worthy of investigation. Testosterone isn’t only important for building muscle or sexual functioning, but also plays a role in metabolic health too.

Testosterone improves insulin sensitivity, which means that it allows the body to use glucose more effectively. Low testosterone has even been implicated in the development of type 2 diabetes. [1] Perhaps it’s no surprise that epidemic of low testosterone has coincided with an epidemic of metabolic diseases in the west. Low testosterone levels are linked to an increase in all cause mortality likely due to increased risk of cardiovascular disease. [2] Boosting this necessary male hormone should be priority even if it weren’t for the desirable effects on muscle and sexual health.

Declining Testosterone

It’s not a myth that testosterone levels have decreased in recent years. It’s a finding that’s been repeated across multiple studies, even across different countries and continents. One study of over 4000 American men measured testosterone levels between 1999 and 2016 found that over this brief period total testosterone in young adults had dropped from an average of 665 ng/dL to 529 ng/dL. [3] This represents a massive 20% decline. Researchers still aren’t exactly sure what is causing this decline, although a number of theories have been proposed.

Phthalates are substances added to plastics to increases their flexibility and durability, and for this reason often end up in clothes, shoes and other consumer products. Troublingly, they are also linked to a reduction in total testosterone, particularly in young men. In boys between 6-12 years old, exposure to phthalate metabolites was associated with a 29% drop in total testosterone. [4] Given how ubiquitous plastic are in our clothing; it’s tempting to think that this could play a role.

Another possible cause for the recent decline in testosterone could be that people no longer smoke. It’s perhaps surprising to learn that something as bad for your health as smoking does in fact boost total and free testosterone levels. One study of over 2000 men between the ages of 20 and 69 discovered that smokers had an average testosterone of 22.3nmol/l versus 20.9nmol/l in nonsmokers. [5]

Whilst nobody should seriously consider taking up smoking to restore their testosterone, these findings do highlight one of the possible mechanisms by which testosterone could be bolstered through more healthy means. Tobacco contains a number of chemicals that inhibit the enzyme that converts testosterone to estrogen called ‘aromatase’. It’s possible that aromatase inhibition could underly the positive effect of smoking on testosterone. [6]

Boghog2, Public domain, via Wikimedia Commons

SHBG and Free Testosterone

Before proceeding with other methods of boosting testosterone, it’s important to recognise that total testosterone isn’t the only measure worth considering. Testosterone can exist in two states: it is either bound to a protein called Sex hormone-binding globulin (SHBG) or Albumin, or it isn’t bound and is referred to as ‘free’. Only around 1-2% of testosterone is ‘free testosterone’ and it’s this testosterone that’s biologically active and can enter cells to activate the androgen receptor.

When testosterone is bound up with SHBG it isn’t biologically active and cannot have an effect. Even if someone were to have a high total testosterone reading, they may still suffer from symptoms of low testosterone if their SHBG was too high. [7] It’s also only free testosterone that’s available to be converted into estrogen by aromatase too, so high SHBG can also mean low estrogen too.

HPTA Axis

The amount of testosterone the body produces, as well as variety of other hormones, is determined by a complex feedback loop called the Hypothalamic-Pituitary-Testicular Axis (HPTA). This is system that interconnects the brain and the gonads to regulate the secretion of testosterone. The Hypothalamus is the hormonal centre of the brain, which monitors the levels of hormones present in the blood.

Artoria2e5, CC BY 3.0 https://creativecommons.org/licenses/by/3.0, via Wikimedia Commons

If the Hypothalamus detects that levels are below optimal it releases gonadotropin-releasing hormone (GnRH) which travels to the pituitary gland. In response the pituitary gland can release Luteinising Hormone (LH) into the blood which directly stimulates testosterone production in the testes using specialised cells called Leydig cells.

In general, there are two types of low testosterone (also called ‘hypogonadism’):

Primary Hypogonadism is where the testes aren’t able to produce adequate testosterone despite normal levels of LH
Secondary Hypogonadism is where the issue resides in the hypothalamus of pituitary gland. People with Secondary Hypogonadism will have low LH and low testosterone, whilst people with Primary Hypogonadism will have high LH but low testosterone levels.

Boosting Testosterone

There are three approaches to boosting natural testosterone levels based on the evidence so far:

Inhibiting the aromatase enzyme which converts testosterone to estrogen
Reducing the levels of SHBG, to increase biologically active ‘free testosterone’
Stimulating greater testosterone synthesis by increasing LH secretion.

Aromatase Inhibition

Aromatase inhibitors are often used in treating cancers in women driven by estrogen such as breast cancer, however there’s also been some investigation into using them in men suffering from hypogonadism. One study of elderly men with low testosterone were treated with a 12-week course of either 1mg or 2mg of anastrozole, and then surveyed from sexual function. [8]

The group taking 1mg experienced an increase in total testosterone from 343 ng/dl to 397 ng/dl, representing a 15% increase. The group taking 2mg went from 397 ng/dl to 520 ng/dl, with a 31% elevation. However, despite these changes, there was not an associated increase in sexual function. However, other studies on Anastrozole have similarly found beneficial effects on testosterone that were matched with improvements in sexual function. [9]

Aromatase inhibitors might be particularly effective in men with a high level of adipose tissue as aromatase is active in body fat. With increased fatty tissue, there is an increase in aromatase and therefor a reduction in testosterone. This has been referred to as ‘hypogonadal–obesity cycle’, as the reduction in testosterone further contributes to the deposition of belly fat. [10]

A number of herbal testosterone boosters commonly found in over-the-counter supplements may be effective by also inhibiting aromatase. Tongkat Ali is the popular name of the Indonesian plant Eurycoma longifolia, which is often touted for being an aphrodisiac. As it turns out, the plant is rich in a variety of bioactive alkaloids which may in fact support this use.

Eurycomanone is found in high concentration in the plant, which has been shown to inhibit aromatase conversion of testosterone to estrogen in Leydig cells. [11] Standardised extracts of Tongkat Ali between 200-400mg increase testosterone in both elderly and young males. [12][13] Tongkat is found especially effective when paired with resistance training. [14]

Reducing SHBG

SHBG can be a tricky topic in regard to hypogonadism for a few reason. High SHBG is generally considered a marker for good health, since very low SHBG can be a symptom of Insulin resistance. [15] SHBG is also beneficial in prolonging the presence of testosterone in the blood, as LH is released as sudden pulses throughout the day which can cause sudden spikes in testosterone.

Nonetheless, high SHBG can give rise to symptoms of low testosterone when it results in comparatively low levels of free testosterone. Interestingly, the element boron is able to lower SHBG and therefore increase free testosterone. One week of 10mg of Boron daily significantly decreased SHBG and increased free testosterone as well as DHT. [16] Boron increased the ratio of free testosterone to total testosterone from 3.62 to 4.66 (pg/mL/ng/mL).[17]

Interestingly, Boron supplementation has even been found to increase free testosterone in athletes during periods of increased training and physical exertion. Just 2mg of Boron daily lead to significant increases in free testosterone following intense exercise. [23]

Clomiphene

Clomiphene is the standard alternative to Testosterone Replacement Therapy in treating Hypogonadism. It works as Selective Estrogen Receptor Modulator (SERM). By blocking the estrogen receptors in the hypothalamus, it tricks the pituitary gland into releasing more LH to produce more testosterone.

Clomiphene is very effective in treating secondary hypogonadism. Just 25mg daily can double average testosterone from 247.6 ng/dL to 610.0 ng/dl in only one month. [18] Since clomiphene treatment both increases testosterone and LH, it also beneficial for fertility purposes. 50mg of clomiphene daily can lead to 2.6-fold increase in sperm concentration. [19]

However, despite its success in increasing testosterone, its impact on sexual functioning is mixed. By occupying the estrogen receptors in the Hypothalamus, it stimulates LH secretion. However, the Estrogen Receptor is vital for regulating Libido. The highest density of Estrogen receptors are in the areas of the brain that most significantly contribute to feeling of sexual desire such as the preoptic area and anterior hypothalamus. [20] This is why Clomiphene treatment, despite increasing testosterone, is sometimes found to paradoxically further lower libido in hypogonadal men. [21]

Conclusion

There are a number of factors that have to be considered when considering how to increase total serum testosterone. Perhaps the best intervention, which doesn’t even require supplementation, is to lower abdominal fat. Belly fat has a high level of aromatase activity, which is going to increase estrogen levels, and further suppresses the HPTA axis by stimulating estrogen receptors in the hypothalamus.

This is perhaps when natural aromatase inhibitors like Tongkat Ali are so effective, since they partially mimic the effect of an ideal body composition on hormonal status. However, aromatase is also critical for general health, and not least cognitive function. Aromatase inhibitors can even block some of the beneficial effects of testosterone administration on visual and verbal memory. [22] Both testosterone and estrogen are needed for optimal physical and mental health.

Boron seems like an ideal natural testosterone booster, by increasing the ratio of free to total testosterone. It’s even been referred to as an ‘androgen amplifier’. It’s present in a number of foods, including raisins and peanuts. However, to reach 10mg of Boron from raisins would require eating around 500g – which isn’t practical. [24] Thankfully 10mg of Boron can easily be obtained from supplements.

This brand offers 240 servings of 10mg of Boron, and purchasing through this link helps to support me.

Clomiphene has mixed results. It’s clearly the most effective option in increasing total testosterone, however in treating the symptoms of low testosterone the results are less clear. This is because it blocks the same estrogen receptors in the hypothalamus that are conducive to sexual functioning. Furthermore, clomiphene citrate is composed of two isomers with different effects.

The shorter acting isomer, enclomiphene, is responsible for blocking occuping the estrogen receptors to stimulate LH secretion. The longer acting isomer, zuclomiphene, is partially estrogenic. This means that over prolonged periods of treatment the zuclomiphene accumulates, increasing the estrogenic activity of the drug. Formulations of pure enclomiphene are being explored, and appear to be a superior alternative.