I’m just going to say what we’ve all been thinking: testosterone is a challenging hormone. It changes the way men and women look and feel if the levels aren’t right. In excess, testosterone stimulates hair growth in places where it isn’t wanted and results in undesirable hair loss on the scalp. Testing can be a challenge because total testosterone in serum doesn’t give us the complete picture of metabolic effects in the body, and right now, that is the standard of care for monitoring testosterone therapy. Moreover, there is no consensus for the best method for raising testosterone levels. Standard of care is to dose testosterone so that the total serum testosterone is within the physiological range, however, this method does not consider testosterone metabolism patterns which can significantly affect how inactive or active that testosterone will be in the body. 

In this brief article, we’ll talk more about these issues surrounding testosterone therapy. We’ll start with how testosterone therapy was discovered and developed, and how we currently think about testosterone therapy. We’ll explore how testosterone is used in both males and females and how it can be safely monitored in clinical settings using “standard of care” and the DUTCH Test. 

History 

The isolation of testosterone began in the 1930s and since then, its use has been rife with controversy in both the public sector and in medical settings. In the 1940s researchers declared that testosterone therapy caused prostate cancer, and it wasn’t until the 1970s when the radioimmunoassay was introduced, the scientific community refuted the claim that the mere presence of testosterone was responsible for prostate cancer. (8) Of course, much of the controversy around testosterone burgeoned with illicit use of anabolic steroids in sporting events. But it took many years for the public to embrace the safety of testosterone when used in carefully controlled medical settings. 

Serum testing for testosterone deficiency in both men and women has been the standard of care since the 1970s, although very few providers at that time would order testing for females. Testing methodologies were radio and direct immunoassays, until recently when (LC-MS/MS) testing gained favor for monitoring sex hormone levels due to its superior specificity, sensitivity, reliability, and high throughput when compared to the immunoassays. In the last two and a half decades salivary assays entered the testing scene and following that, ultra-sensitive urine assays that included analysis of androgen metabolites were introduced in the functional medicine space. The urine assays give providers a more comprehensive look at how patients break down androgens and therefore enrich the development of more informed treatment plans for patients. 

Significant levels of testosterone are found in all adults and its importance in health cannot be overstated. Androgen receptors are found throughout the body and influence all aspects of endocrine, cardiovascular, neurological, reproductive, and musculoskeletal functions. 

Historically, testosterone was thought of as a “male” hormone but fortunately, there is a movement to emphasize female sexual health and its connection to androgen production. Whatever part of the gender spectrum you’re on, testosterone is important. It can be said that as testosterone concentration in the body increases, we see an increase of what we think of as “male attributes.” This may be desirable for some individuals, or it may create unwanted symptoms. Regardless, as testing methodologies and offerings improve, we can expect to be able to optimize levels and health outcomes. 

In men, we mostly test for deficiency. Hypogonadism and andropause are estimated to affect 10% of men older than 30 years of age and up to 40% of men older than 70 years of age.(7) Despite its prevalence, it is estimated that only 5-10% of men with low testosterone are being treated! (4) These statistics illuminate the gap between diagnosis and treatment for men and certainly give us a mandate to improve opportunities for diagnosis and treatment of hypogonadism. 

There are quite a few useful tools when assessing the need to test testosterone in males and the ADAM questionnaire shown below is one of them. A positive score is indicated by answering "yes" to either question 1 (decrease in libido) or question 10 (less strong erections), or by answering "yes" to any three other questions. 

Male and Female Assessments

Less common but still important is assessing male sexual health by looking at androgen metabolism patterns, specifically the balance between the more potent, more androgenic alpha metabolites and the less potent, less androgenic beta metabolites. Males with lower alpha testosterone metabolites (5a-DHT, 5a-androstanediol) may be prone to the testosterone deficiency symptoms mentioned above. 

When it comes to female health, until recently, the medical community has been slow to turn the tide in the diagnosis and treatment of sexual dysfunction as it relates to low testosterone and overall low androgens. 

Here at DUTCH, we are working to improve that, and a high percentage of our testing is done on female patients. For females, symptoms of low testosterone include: 

• Low libido 
• Decreased arousal 
• Inability to orgasm 
• Low motivation 
• Anxiety  
• Depression  
• Lack of well-being 
• Fatigue 
• Loss of muscle mass and strength 
• Difficulty concentrating 
• Irregular menses (premenopausal women) 
• Vaginal dryness 
• Sleep disturbances 
• Thinning hair and dry skin 
• Weight gain or weight loss resistance 
• Infertility or difficulty conceiving 

Testing 

The standard of care for testing for both males and females includes total testosterone level, followed by a free testosterone test in serum or a calculated value derived from measuring total testosterone combined with albumin and sex hormone binding globulin (SHBG). Taking an advanced look at testing for androgen deficiency and replacement therapy can be done with the DUTCH Test. DUTCH offers a comprehensive look at the hormones in the androgen pathway including testosterone, and the direct metabolites, 5a-DHT and 5b-androstanediol and 5a-androstanediol. Along with testosterone metabolites, we look at DHEAs, etiocholanolone, androsterone, and epi-testosterone to help us assess total body output of the anabolic steroids. 

Replacement Options 

After a full assessment using the tools mentioned above, treatment options for low testosterone can be considered. Standard of care dictates that testosterone therapy is an obvious choice for both males and females under the right circumstances. Popular options include transdermal, injectables, and pellet therapy. Depending on the patient’s age, sex, cycling status, comorbidities, risk factors, etc., dosing is determined, and therapy is monitored as mentioned above.   

Supportive Therapies 

Non-hormone therapy considerations for optimizing levels of testosterone and improving overall androgen status, include optimizing nutritional status with zinc and boron, improving circadian rhythms and sleep cycles, gut health, strength and fitness, and reduction of inflammation and stress. Some small studies have shown mild improvement in testosterone levels when using herbal therapies as well. Our new DUTCH Treatment Guide can be found on your Provider Portal, and this will give you some insight into available supportive options. This resource is exclusive to registered DUTCH Providers. If you're not yet a DUTCH Provider, become one today! 

Androgen Excess in Women 

While most of this article refers to replacement therapy, testing for endogenous androgen excess should not be ignored. When correlated with symptoms, looking at the total androgen picture in blood and urine allows one to see how the testosterone is metabolized and get a more comprehensive understanding of how to best treat the patient for optimal clinical outcomes. We have an insightful white paper available on 5a-androstanediol as a marker of androgen status in female patients – read it here. 

In summary, some things to think about when assessing patients’ androgen status: 

1. Understand the standard of care assessments and treatments regarding androgen status. 
2. Use standard of care testing along with the DUTCH Test to optimize the chance for better treatment outcomes. 
3. Look at the relationship between all the sex hormones and consider that imbalance may be the most important factor in how the patient feels. 
4. Use standard of care treatments where appropriate for the individual patient with the minimal effective dose according to clinical signs and symptoms and laboratory assessment. 
5. Use supportive therapies and optimized lifestyle factors for the best chance of restoring normal levels if standard of care is not used. 

We admit that testosterone therapy can be a problematic hormone to deal with, but it offers so many benefits when used within the confines of standard of care. Additionally, DUTCH testing can offer additional insight into androgen deficiency or excess symptoms by providing a look into androgen metabolism patterns. 

Become a DUTCH Provider to gain access to free educational resources, comprehensive patient reports, expert clinical support, and validated and peer-reviewed research.

References

1. Abraham Morgentaler, Abdulmaged Traish, The History of Testosterone and the Evolution of its Therapeutic Potential, Sexual Medicine Reviews, Volume 8, Issue 2, 
2. 2020, Pages 286-296, ISSN 2050-0521, . 
3. (https://www.sciencedirect.com/science/article/pii/S2050052118300404) 
4. Carruthers M. Time for international action on treating testosterone deficiency syndrome. Aging Male 2009; 12:21-28. [DOI] [PMC free article] [PubMed] [Google Scholar] 
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6. Krakowsky Y, Grober ED. Testosterone Deficiency - Establishing A Biochemical Diagnosis. EJIFCC. 2015 Mar 10;26(2):105-13. PMID: 27683486; PMCID: PMC4975356. 
7. Liu PY, Beilin J., Meier C., et al. Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohort. J Clin Endocrinol Metabolism 2007; 92:3599-3603. 
8. Rostom M, Ramasamy R, Kohn TP. History of testosterone therapy through the ages. Int J Impot Res. 2022 Nov;34(7):623-625. doi: 10.1038/s41443-021-00493-w. Epub 2022 Jan 24. PMID: 35075296.