Hypogonadism, also known as testosterone deficiency, is increasing in prevalence worldwide. While a rapidly expanding body of research is documenting the detrimental health consequences of hypogonadism, at the same time there is a prevailing concern and misunderstanding about the effects of testosterone therapy on cardiovascular risk.
In this article I present a summary of a recently published comprehensive review on the association of hypogonadism with cardiovascular risk factors, and the effect of testosterone therapy on those risk factors.
Testosterone deficiency, also known as hypogonadism, is gaining recognition among both clinicians and the general population. This article summarizes the findings from a review on the prevalence of testosterone deficiency, as well as the proportion of hypogonadal men who are receiving testosterone treatment.
While testosterone prescribing has increased lately, as you will find out here, the prevalence of testosterone deficiency far exceeds the prescribing rate; i.e. majority of men with low-T are still not being treated with testosterone therapy.
You may be surprised to find out that testosterone deficiency is still not well-understood by general practitioners and cardiologists, and that these key clinicians lack knowledge on its deleterious cardiovascular effects. Therefore, even man needs to take control of his own health and don't let any ignorant or old-school doctor deny you a prescription that you may need...
In a previous article I outlined a study showing the effectiveness of testosterone therapy on menopausal symptoms in pre- and post-menopausal women. Here I will present and comment on an insightful study that compared head-to-head the effectiveness of testosterone therapy and estrogen therapy in surgically menopausal women who had their ovaries removed.
Before the surgical removal of both ovaries (bilateral ovariectomy) women were randomly assigned to either a testosterone alone, estrogen alone, or placebo groups. There were 10 patients in each group.
Mean age of the women was 46 years. They had underwent bilateral ovariectomy due to having uterine fibroids (aka myoma), which are non-cancerous (benign) tumors that develop in the womb (uterus).
The testosterone group received injectable testosterone (enanthate); 200 mg/ml.
The estrogen group received injectable estradiol; 10mg/ml.
The testosterone/estrogen group received injectable testosterone (enanthate) 150 mg + 8.5 mg estradiol/ml.
All groups received 1 ml intramuscular injections every 28 days for 3 months.
Testosterone levels in women decline steeply with age during the reproductive years; by the time women reach their late 40, their blood testosterone levels are approximately half what they were in their 20s.[1, 2]
Testosterone deficiency, also known as hypogonadism, is a state with sub-optimal circulating levels of testosterone concomitant with clinical signs and symptoms attributed to low physiological testosterone levels.[1-3]
Sexual dysfunction is the most commonly recognized symptom of testosterone deficiency. However, testosterone also plays a broader role in men's health. A growing body of evidence has established associations between low testosterone levels and multiple risk factors and diseases including the metabolic syndrome, obesity, type-2 diabetes, sarcopenia, frailty, mobility limitations, osteoporosis, cognitive impairment, depression, cardiovascular disease, and reduced longevity.[3-12]
This summary gives an overview of the detrimental impact of testosterone deficiency on a wide range of health outcomes.
Testosterone therapy has been in use for more than 70 years for the treatment of testosterone deficiency, historically called hypogonadism.In the past 30 years there has been a growing body of scientific research demonstrating that testosterone deficiency is associated with increased body weight/adiposity/waist circumference, insulin resistance, type 2 diabetes, hypertension, inflammation, atherosclerosis and cardiovascular disease, erectile dysfunction (ED) and increased risk of mortality [2, 3]. In line with the detrimental health outcomes seen with testosterone deficiency, testosterone therapy has been shown to confer beneficial effects on multiple risk factors and risk biomarkers related to these clinical conditions.
Despite these well-documented health benefits, testosterone therapy is still controversial, in large part due to a few flawed studies and media outcry about potential elevated heart attack risk with testosterone therapy. On July 2, 2014, a study was published which demonstrated that testosterone therapy is not associated with an increased risk of MI, and that is actually may protect against heart attack....
Alleged concerns regarding risk of cardiovascular disease with testosterone replacement therapy (TRT) have been promulgated recently. However, a large and growing number of intervention studies show to the contrary that TRT reduces cardiovascular risk factors and confers multiple beneficial health effects. Thus, fears promoted by some recent flawed studies need to be critically re-evaluated.
This article gives an overview of studies that have investigated health effects and safety of TRT. As outlined here, the position that testosterone deficiency (TD) should be regarded as a risk factor for cardiovascular disease is supported by a rapidly expanding body of evidence.[2-4]
A long-held belief is that testosterone stimulates development of prostate cancer and/or accelerates its growth. This fear is the most common reason for doctors' reluctance to prescribe testosterone replacement therapy, even in hypogonadal men [1, 2] , which unnecessarily deprives many hypogonadal men of clinical benefits.
This summary gives an overview of an in-depth review of current literature regarding the relationship of testosterone levels and prostate cancer, and the effect of testosterone replacement therapy on prostate cancer progression and recurrence. Key studies which have refuted the old belief that testosterone has harmful effects on the prostate are presented, along the new testosterone-prostate paradigm known as the saturation model.
Surprisingly, new research provocatively suggests that it is not high testosterone levels that are problematic for prostate cancer, but to the contrary that it is low serum T that is associated with worrisome cancer features and outcomes...and new experimental research has uncovered mechanisms that explain how low testosterone levels may be detrimental for prostate health, and support the new view that testosterone therapy actually may have beneficial effects with regard to prostate cancer...
In part 1 - "TRT and Fertility – how to get the best of both worlds" - I covered issues related to the effect of TRT (Testosterone Replacement Therapy) on male fertility. Here I will outline options for men to increase endogenous testosterone production by non-TRT means, and ways to speed up spermatogenesis for those who chose to go the TRT route...
The same strategies apply to increasing endogenous testosterone production and speeding up its recovery after supplementation, as illustrated in the figure:
The prevalence of testosterone deficiency (aka hypogonadism or Late Onset Hypogonadism), defined as total testosterone (TT) at or below 300 ng/dl is close to 40% in men aged 45 years and older presenting to primary care offices in the US. Year 2006 is was estimated that more than 13.8 million men over 45 years of age visiting a primary care doctor in the United States have symptomatic androgen deficiency.
A large international web survey using the Aging Males' Symptoms (AMS) questionnaire showed the prevalence of symptomatic testosterone deficiency to be 80% in men aged 16–89 (mean 52 years). It is notable that in the survey 40% of respondent were at younger ages when ‘Late Onset Hypogonadism’ is generally not believed to be occurring. The surprisingly high prevalence of raised scores indicating testosterone deficiency in the younger age groups may be due to the increasing prevalence of conditions in these age groups known to reduce testosterone levels, such as obesity [3-7] and chronic work stress. [8-10] Stress induced cortisol elevation, by increasing SHBG, lowers the free active fraction of testosterone and thereby reduces its action.
This large and rising prevalence of testosterone deficiency is gaining recognition among doctors and patients alike. However, while testosterone replacement therapy (TRT) confers great benefits to men with sup-optimal testosterone levels, it also comes with some side-effects which are especially relevant for men who wish to have a family...Many testosterone users and even clinicians  are unaware that exogenous testosterone suppresses the hypothalamic-pituitary-gonadal (HPG) axis and may result in infertility...however, in most cases, TRT induced infertility is reversible. If paternity is of interest to you, read on...