Sexual Health

Low Testosterone (Male Hypogonadism) Treatment

Testosterone is a sex hormone that is  responsible for androgenesis and facilitating puberty in boys. Testosterone is produced by specialised cells in the testicles – Leydig cells.

Testosterone  enables the maintenance of male reproductive organs throughout adulthood. Indeed, castration before puberty leads to the regression  of the male reproductive organs.

Most testosterone is produced in the testicles from cholesterol and acetic acid. The adrenal glands also contribute to the production of testosterone. It is important to note that some testosterone is converted into estrogen. Testosterone and estrogen co-exist in both men and women.

Estrogen is essential for the maturation of sperm and maintenance of libido in men (Tyagi et al., 2017). Even though women do not have testicles, they are capable of producing some testosterone in bone, breast, muscle, and fat cells.

There has been an interest in testosterone ever since the Massachusetts Male Aging Study. This study demonstrated that testosterone declines with increasing age (Gray et al., 1991). The secretion of testosterone follows a circadian rhythm in both young and aging men. The highest levels of testosterone occur in the early morning hours, whereas the lowest levels occur in the evening. 

The Role of Testosterone

Testosterone is most known for its effects on sexual function. Testosterone leads to the development of male secondary sexual characteristics.

Yet, it has many other roles which are critical for the normal functioning of the human body. These include (Bain, 2007):

  • Bone density and strength

  • Cognitive capacity and processing speed

  • Mood

  • The generation of healthy red blood cells (erythropoiesis)

Why is Testosterone Used?

There are a number of reasons why transdermal testosterone is used in medicine today.

Testosterone has significant effects on the musculoskeletal system. These include (Tyagi et al., 2017). :

  • Muscular strength: Testosterone maintains and promotes lean muscle mass, strength, and size.

  • Muscular size: Testosterone has been shown to have beneficial effects on lean muscle mass and body fat. These musculoskeletal benefits are not exclusive to young men. One randomized controlled trial recruited older men between the ages of 60 and 78.

    Researchers subjected them to strength training, testosterone therapy, and sham therapy for 24 weeks. They found that strength training in older men with low-normal testosterone levels improved muscle function but not lean body mass. Combined with testosterone, however, strength training led to increased muscle function and mass.

  • Bone strength: Testosterone boosts the endogenous levels of Vitamin D, leading to improved bone strength.

  • Body fat: An elevated testosterone level also prevents the accumulation of body fat (Finkelstein et al., 2013).

Further uses:

In addition to the musculoskeletal effects of testosterone, physicians prescribe this male hormone for other reasons as well.

  • Chronic disease: Patients with chronic diseases such as cancer and human immunodeficiency virus (HIV) suffer debilitating muscle wasting. This leads to significant weakness and frailty. Clinicians administer testosterone to these patients to preserve muscular strength and function (Finkelstein et al., 2013).

  • Urinary symptoms: Older men who have an enlarged prostate gland due may also suffer from obstructive urinary symptoms. Testosterone supplementation in this group of men improves these storage and voiding symptoms (Ko et al., 2013). 

  • Mood disorders: It may surprise some readers that testosterone is also prescribed for mood disorders. Testosterone plays a crucial part in modulating cognitive functioning and mental health.

    One randomized controlled trial demonstrated that 100mg of weekly testosterone for 6 weeks resulted in a significant improvement in spatial and verbal memory. The participants in this study were healthy older men (Cherrier et al., 2001).

    In men with a documented and known testosterone deficiency, the administration of testosterone supplements has been associated with a decrease in negative mood parameters (Wang et al., 1996). These negative mood parameters include nervousness, anger, and irritability. The administration of testosterone in men with low to normal levels of testosterone results in an improvement in positive mood parameters and wellbeing. 

How Does Testosterone Work?

The hypothalamus secretes GnRH, which travels to the pituitary gland and stimulates the release of LH and FSH. The hypothalamus pulses every 1 to 3 hours to release GnRH. LH acts on the Leydig cells within the testicles to stimulate the production and secretion of testosterone.

In the Leydig cells, cholesterol and acetic acid are converted into testosterone. Most of the testosterone is bound to proteins such as sex-hormone-binding-globulin (SHBG) and albumin.

The rest of the testosterone remains free in the bloodstream and acts on peripheral tissues such as bone, muscle, and the prostate gland. Testosterone is converted into dihydrotestosterone (DHT) by a specific enzyme known as 5-alpha-reductase.

Both testosterone and DHT bind to cell surface receptors and regulate the expression of proteins. Testosterone works on target cells in one of three ways. First, testosterone acts like estrogen when it is converted by aromatase to estradiol. Second, testosterone acts on the androgen receptors. Third, testosterone is converted to DHT by 5-alpha-reductase and operates in target tissues.

Testosterone Side Effects

Despite the benefits of testosterone, there are several side-effects of testosterone supplementation. These side effects can range from being common and mild, to uncommon and severe.

We have listed these side effects for our readers to be mindful of when deliberating testosterone supplementation. Many of the side effects of testosterone are dependent on the formulation of testosterone administered.

Testosterone gels and intramuscular injections are the most common formulations. But, other trans-dermal formulations such as patches, solutions, and pellets also exist. Trans-dermal testosterone patches are usually applied to the back, abdomen, thigh, or upper arms.

Mild Side Effects:

  • Skin irritation (dermatitis)

  • Skin hyper-pigmentation

  • Allergic reaction

Moderate-Severe Side Effects:

Cardiovascular morbidity and mortality

  • Reduced testosterone levels are associated with an increased risk of the development of cardiovascular disease.

  • Evidence of an elevated risk of heart disease because of testosterone supplementation is conflicting

  • One recent meta-analysis found that testosterone supplementation increased the risk of cardiovascular events (e.g., heart attacks) (Xu et al., 2013)

  • Another study found that testosterone replacement therapy led to a 6% increased risk of mortality, heart attack or stroke in 1223 men (Vigen et al., 2013)

  • In another study dubbed as The Testosterone in Older Men (TOM) trial, 209 men with a mean age of 74 years were prescribed with testosterone replacement.

  • Even though the older men experienced significant improvements in chest and leg strength, the study was discontinued.

  • This is because the researchers observed a higher incidence of adverse cardiovascular events (e.g., heart attacks) among the participants (Basaria et al., 2010)

Elevation of Prostate-Specific Antigen (PSA)

  • The researchers found that testosterone patch therapy for men with testosterone deficiency led to an increase in the PSA level (Raynaud et al., 2013)

Obstructive Sleep Apnea

  • One randomized controlled trial found that testosterone replacement therapy in obese men with obstructive sleep apnoea.

  • The researchers observed that testosterone resulted in a worsening of their sleep-disordered breathing.

  • Even though testosterone improved the insulin resistance and liver fat profile of these participants, it did not reduce their weight.

Raised Red Blood Cell and Platelet Counts

  • One meta-analysis which evaluated 11 independent trials, found that testosterone therapy increases the red blood cell and platelet counts.

  • Theoretically, this would increase the risk of stroke or clots in the lower limbs.

  • However, there is no evidence to prove this link, so the risk remains theoretical.

Interactions With Other Medications

Individuals who are administered with testosterone should be aware of these potential drug-drug interactions.

Drug-drug interactions can cause the accumulation of bioactive drug metabolites and cause liver or renal impairment. They may also potentiate the adverse effects of one another (Berkseth et al., 2016). 

  • Zolpidem

  • Aspirin
  • Clomiphene

  • Rosuvastatin

  • Duloxetine

  • Finasteride

  • Insulin

  • Escitalopram

  • Atorvastatin

  • Pregabalin

  • Levothyroxine

  • Esomeprazole

  • Sildenafil

  • Alprazolam

  • Sertraline

  • Cetirizine

Testosterone Warnings

There are several warnings and contra-indications to testosterone replacement therapy. These include (Bassil et al., 2009):

  • History of breast cancer (men can have breast cancer too)

  • Prostate cancer

  • Uncontrolled heart failure

  • History of a heart attack or stroke within the last six months

  • Obstructive sleep apnoea

  • Men planning to have children

  • A nodule in the prostate gland

  • An elevated PSA (>4 ng/mL)

How To Take Testosterone

Transdermal Gel

  • Applied to the shoulder, upper arms, abdomen, or thigh

  • A novel nasal gel is available that is applied three times daily

  • Should not be applied to the scrotum

Intramuscular Injections

  • Include testosterone enanthate and testosterone cypionate

  • Dosed at 50-100mg evert week or 100-200mg every two weeks

Transdermal Patch

  • Applied to the back, abdomen, thigh or upper arm

  • Should not be applied to the scrotum

Transdermal Pellet

  • Pellets are placed under the skin of the buttocks, abdominal wall, or thigh

  • These are placed every three to six months

It should be noted that testosterone is rarely administered orally. This is because oral formulations are ineffective and can lead to liver damage in the long term. Buccal tablets that are prescribed are meant to be absorbed through the gums, and not chewed or swallowed. 

Factors to Consider when Taking Testosterone

Individuals who are prescribed with testosterone must be vigilant, and factor in the follow considerations:

  1. Monitoring of blood testosterone level one month after commencing treatment

  2. Liver function test, lipid levels, PSA level and Blood Pressure monitoring 3-6 months after commencing treatment

  3. Annual checks after one year of continuous therapy:
  • Liver function

  • Lipid levels

  • PSA levels

  • Digital Rectal Examination by a licensed Physician

  • Estradiol levels

  • Blood Pressure

  • Complete Blood Count

How to Naturally Increase Testosterone

There are several ways in which testosterone levels can be boosted naturally. One of these ways is by taking naturally occurring compounds as supplements.

  • Ginseng (Leung and Wong, 2013)

  • Ashwagandha (Lopresti et al., 2019)

  • Fenugreek (Wankhede et al., 2016)

  • Ginger (Banihani, 2018)

  • Zinc (Liu et al., 2017)

Another strategy that men can undertake is that of aerobic exercise. Evidence suggests that cardiorespiratory exercise in any form can reduce body fat percentage and increase serum testosterone levels, regardless of age (Yeo et al., 2018). 

At Ben’s Natural Health, we have formulated our very own proprietary blend of all-natural supplements. These supplements safely and effectively boost testosterone levels in men. Ben’s Testo-Booster consists of time-tested natural compounds:

  • Tongkat Ali

  • Maca Root

  • Ashwagandha

  • Oatstraw

  • Black Pepper Fruit

  • Tribulus terrestris

  • Yohimbine 

Conclusion

Testosterone deficiency is a highly prevalent problem among older men. Younger men who seek athletic enhancements also administer testosterone to realize muscular gains.

Nevertheless, testosterone supplementation and replacement are associated with several long-term adverse outcomes. Men are encouraged to seek out natural and effective means of boosting their testosterone levels. They should do so before seeking out synthetic testosterone regardless of the formulation.

Sources

  1. Bain, J. (2007) ‘The many faces of testosterone’, Clinical interventions in aging, 2(4), pp. 567-576.
  2. Banihani, S. A. (2018) ‘Ginger and Testosterone’, Biomolecules, 8(4), pp. 119.
  3. Basaria, S., Coviello, A. D., Travison, T. G., Storer, T. W., Farwell, W. R., Jette, A. M., Eder, R., Tennstedt, S., Ulloor, J., Zhang, A., Choong, K., Lakshman, K. M., Mazer, N. A., Miciek, R., Krasnoff, J., Elmi, A., Knapp, P. E., Brooks, B., Appleman, E., Aggarwal, S., Bhasin, G., Hede-Brierley, L., Bhatia, A., Collins, L., LeBrasseur, N., Fiore, L. D. and Bhasin, S. (2010) ‘Adverse events associated with testosterone administration’, N Engl J Med, 363(2), pp. 109-22.
  4. Bassil, N., Alkaade, S. and Morley, J. E. (2009) ‘The benefits and risks of testosterone replacement therapy: a review’, Therapeutics and clinical risk management, 5(3), pp. 427-448.
  5. Berkseth, K. E., Thirumalai, A. and Amory, J. K. (2016) ‘Pharmacologic Therapy in Men’s Health: Hypogonadism, Erectile Dysfunction, and Benign Prostatic Hyperplasia’, The Medical clinics of North America, 100(4), pp. 791-805.
  6. Cherrier, M. M., Asthana, S., Plymate, S., Baker, L., Matsumoto, A. M., Peskind, E., Raskind, M. A., Brodkin, K., Bremner, W., Petrova, A., LaTendresse, S. and Craft, S. (2001) ‘Testosterone supplementation improves spatial and verbal memory in healthy older men’, Neurology, 57(1), pp. 80-8.
  7. Finkelstein, J. S., Lee, H., Burnett-Bowie, S. A., Pallais, J. C., Yu, E. W., Borges, L. F., Jones, B. F., Barry, C. V., Wulczyn, K. E., Thomas, B. J. and Leder, B. Z. (2013) ‘Gonadal steroids and body composition, strength, and sexual function in men’, N Engl J Med, 369(11), pp. 1011-22.
  8. Gray, A., Feldman, H. A., McKinlay, J. B. and Longcope, C. (1991) ‘Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study’, J Clin Endocrinol Metab, 73(5), pp. 1016-25.
  9. Ko, Y. H., Moon du, G. and Moon, K. H. (2013) ‘Testosterone replacement alone for testosterone deficiency syndrome improves moderate lower urinary tract symptoms: one year follow-up’, World J Mens Health, 31(1), pp. 47-52
  10. Leung, K. W. and Wong, A. S. (2013) ‘Ginseng and male reproductive function’, Spermatogenesis, 3(3), pp. e26391-e26391.
  11. Liu, Y.-L., Zhang, M.-N., Tong, G.-Y., Sun, S.-Y., Zhu, Y.-H., Cao, Y., Zhang, J., Huang, H., Niu, B., Li, H., Guo, Q.-H., Gao, Y., Zhu, D.-L., Li, X.-Y. and Hypogonadotropic Hypogonadism Intervention Study, G. (2017) ‘The effectiveness of zinc supplementation in men with isolated hypogonadotropic hypogonadism’, Asian journal of andrology, 19(3), pp. 280-285.
  12. Lopresti, A. L., Drummond, P. D. and Smith, S. J. (2019) ‘A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Examining the Hormonal and Vitality Effects of Ashwagandha ( Withania somnifera) in Aging, Overweight Males’, American journal of men’s health, 13(2), pp. 1557988319835985-1557988319835985.
  13. Raynaud, J. P., Gardette, J., Rollet, J. and Legros, J. J. (2013) ‘Prostate-specific antigen (PSA) concentrations in hypogonadal men during 6 years of transdermal testosterone treatment’, BJU Int, 111(6), pp. 880-90.
  14. Tyagi, V., Scordo, M., Yoon, R. S., Liporace, F. A. and Greene, L. W. (2017) ‘Revisiting the role of testosterone: Are we missing something?’, Reviews in urology, 19(1), pp. 16-24.
  15. Vigen, R., O’Donnell, C. I., Barón, A. E., Grunwald, G. K., Maddox, T. M., Bradley, S. M., Barqawi, A., Woning, G., Wierman, M. E., Plomondon, M. E., Rumsfeld, J. S. and Ho, P. M. (2013) ‘Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels’, Jama, 310(17), pp. 1829-36.
  16. Wang, C., Alexander, G., Berman, N., Salehian, B., Davidson, T., McDonald, V., Steiner, B., Hull, L., Callegari, C. and Swerdloff, R. S. (1996) ‘Testosterone replacement therapy improves mood in hypogonadal men–a clinical research center study’, J Clin Endocrinol Metab, 81(10), pp. 3578-83.
  17. Wankhede, S., Mohan, V. and Thakurdesai, P. (2016) ‘Beneficial effects of fenugreek glycoside supplementation in male subjects during resistance training: A randomized controlled pilot study’, Journal of sport and health science, 5(2), pp. 176-182.
  18. Xu, L., Freeman, G., Cowling, B. J. and Schooling, C. M. (2013) ‘Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials’, BMC Med, 11, pp. 108.
  19. Yeo, J. K., Cho, S. I., Park, S. G., Jo, S., Ha, J. K., Lee, J. W., Cho, S. Y. and Park, M. G. (2018) ‘Which Exercise Is Better for Increasing Serum Testosterone Levels in Patients with Erectile Dysfunction?’, The world journal of men’s health, 36(2), pp. 147-152.

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