Testosterone Deficiency: Linking Weakness and Multimorbidity in Men

Posted by Brianna Clark, Updated on October 17th, 2023
Reading Time: 4 minutes

The male hormone testosterone is required for a variety of physiological processes, including muscular growth, bone health, and overall well-being. Because it has been related to a variety of health issues in men, testosterone deficiency, also known as hypogonadism, is a disease characterized by lower-than-normal testosterone levels. The complicated link between low testosterone and male obesity, frailty, and multimorbidity is investigated in this study. 

We look at the epidemiology, etiology, clinical symptoms, diagnostic criteria, and therapies for low testosterone. We also examine the accumulating evidence that testosterone deficiency weakens people and contributes to the formation of various comorbid disorders, emphasizing the need for early identification and treatment.


Testosterone is a critical hormone that governs a multitude of physiological processes in males, including muscular growth and strength, bone density, mood, and sexual function. It is primarily produced in the testes. Naturally, testosterone levels decline as men age, but in certain cases, the decline is substantial, resulting in hypogonadism or testosterone insufficiency. A variety of testosterone deficiency symptoms have been linked to an increased risk of a variety of disorders, including weakness and multimorbidity. The purpose of this research is to conduct an in-depth analysis of testosterone deficiency's prevalence, etiology, clinical consequences, and role in men's frailty and multimorbidity.

Age-Related Testosterone Deficiency in Men: Implications for Health and Well-being

According to 2011 data, testosterone has become one of the most often prescribed drugs in the United States, with prescriptions growing fivefold. This development has resulted in a substantial expansion in the pharmaceutical industry's testosterone replacement treatment (TRT) sector, which has grown from US$18 million in the 1980s to US$1.6 billion in 2011. The explanation is numerous, but it may be linked in part to the ongoing rise of the over-65 population and a growing awareness of medical comorbidities associated with low testosterone, such as metabolic syndrome (MetS) and cardiovascular disease (CVD). [1]

After age 30, testosterone levels start to drop quickly (by up to 2% yearly), with 35% of men in their seventh decade having lower testosterone levels than younger men and 13% of men over the age of 60 meeting the diagnostic criteria for hypogonadism. This has caused a subset of men with hypogonadism, known as "late-onset" hypogonadism (LOH) or andropause, to develop who are older than 65 years old.

Male adult reproductive health, sexual function, bone health, fat metabolism, and muscular mass and strength are all significantly influenced by testosterone. The hypothalamic-pituitary-gonadal (HPG) axis tightly controls the synthesis of testosterone by testicular Leydig cells through the release of luteinizing hormone (LH). Primary, secondary, or mixed hypogonadism can develop from failure to maintain this delicate equilibrium.

Due to a variety of factors, the prevalent type of testosterone deficiency (TD) in older men combines elements of primary and secondary hypogonadism. LH levels in elderly men might fluctuate depending on factors such as decreasing Leydig cell numbers and function, decreased HPG axis sensitivity to feedback inhibition, and/or lower LH pulse amplitude despite normal pulse frequency.

Diagnostic Criteria for Testosterone Deficiency:

Due to the absence of high-quality, randomized studies in older men, the diagnosis of TD in aging men is predicated on the presence of both clinical symptoms and low blood testosterone levels, similar to the method employed in younger or middle-aged men. However, due to the prevalence of symptoms related to normal aging that coincide with those associated with TD, diagnosing TD in older males is more challenging. However, due to the obvious age-related decline in testosterone levels, assessing individuals for biochemical TD alone might result in a considerable overdiagnosis.

In actuality, many older men with 'low testosterone' don't even exhibit any symptoms. Due to this conundrum, several influential medical associations and organizations have defined LOH as a clinical and biochemical condition that is linked to aging, manifested by symptoms, and characterized by blood testosterone levels below those of young, healthy guys. Due to these factors, during the first examination, specified etiologies of primary and secondary symptomatic hypogonadism must be distinguished from LOH; otherwise, the apparent low testosterone may just be a normal physiological reaction to age.

Laboratory testing is necessary to confirm the diagnosis of hypogonadism in older men who exhibit its signs or symptoms. Due to diurnal variance, initial testing should include a total blood testosterone level collected between 7 a.m. and 11 a.m. However, a considerable percentage of older men might experience blunting of the diurnal fluctuation, and up to 30% of individuals with initially abnormal findings will have normal levels on subsequent testing. [2]


According to Pearson-Stuttard et al. (2019), one of the biggest current and upcoming issues for healthcare systems is multimorbidity. However, the definition of the word "multimorbidity" is still up for debate. [3]

 The phrase evokes a wide range of interpretations, including but not limited to:

  • the coexistence of several aging-related health issues among older persons, which is linked to (and implicitly caused by) an aging global population;
  • The early development and widespread occurrence of complicated, long-term mental and physical health disorders that are made worse by unfavorable socioeconomic circumstances. This type of multimorbidity emphasizes how disease and societal hardship reinforce one another;
  • The co-existence of two or more chronic illnesses in one individual whose demands are not completely satisfied by care systems that are set up on a "single disease" approach. Multimorbidity is not seen as a stable entity in this theory but rather as an "avatar for the fundamental, recurring problems of modern medicine and the organization of care," according to Lefèvre and colleagues.


The complicated and multidimensional illness of testosterone shortage can significantly affect the health and well-being of men. It is linked to a variety of testosterone deficiency symptoms, such as mood swings, sexual dysfunction, and physical weakness. A lack of testosterone may also lead to the emergence of multimorbidity, which includes cardiovascular disease, metabolic syndrome, obesity, type 2 diabetes, and osteoporosis, according to new research.

To lessen the symptoms of testosterone insufficiency and enhance the general health and quality of life of afflicted people, early identification and adequate care of the condition are crucial. Clinicians should carefully assess patients who exhibit signs of low testosterone while taking into account the possible advantages and disadvantages of testosterone replacement treatment on an individual basis. To completely understand the intricate interactions between low testosterone and multimorbidity and to improve therapy approaches for this illness, more study is required.

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