Male Hormone RestorationThe significance of testosterone for male sexual function is apparent to most Life Extension customers. New insights, however, underscore the critical role testosterone plays in maintaining youthful neurological structure, alleviating depression, as well as inducing fat loss in those who are unable to reduce body weight regardless of diet and exercise. Recent studies have demonstrated that low testosterone in men is strongly associated with metabolic syndrome, type 2 diabetes, cardiovascular disease (Miner and Seftel 2007), and an almost 50% increase in mortality over a seven year period (Malkin et al 2010). Restoring testosterone to youthful ranges in middle-aged, obese men resulted in an increase in insulin sensitivity as well as a reduction in total cholesterol, fat mass, waist circumference and pro-inflammatory cytokines associated with atherosclerosis, diabetes, and the metabolic syndrome (Kapoor et al 2006, Malkin et al 2004, Heufelder et al 2009). Testosterone therapy also significantly improved erectile function (Fukui 2007) and improved functional capacity, or the ability to perform physical activity without severe duress, in men with heart failure (Malkin et al 2007).
Factors That Affect Testosterone Levels in MenDHEA: Dehydroepiandrosterone (DHEA) is a hormone produced from cholesterol that then follows one of two pathways, both involving two-step enzymatic conversions, to yield either estrogens or testosterone. Thus, levels of DHEA can have a role in determining levels of estrogen and testosterone, though DHEA alone is seldom enough to sufficiently restore testosterone levels in aging men. Aromatase: One of the most important factors that affect testosterone levels and the ratio between testosterone and estrogen is the aromatase enzyme. Aromatase converts testosterone to estrogen, further depleting free testosterone levels and increasing estrogen levels. Obesity: Obesity and associated hyperinsulinemia suppress the action of luteinizing hormone (LH) in the testis, which can significantly reduce circulating testosterone levels (Mah and Wittert 2010), even in men under the age of 40 (Goncharov et al 2009). In addition, increased belly fat mass has been correlated with increased aromatase levels (Kalyani and Dobs 2007). The vicious circle of low testosterone and obesity has been described as the hypogonadal/obesity cycle. In this cycle a low testosterone level results in increased abdominal fat, which in turn leads to increased aromatase activity. This enhances the conversion of testosterone to estrogens, which further reduces testosterone and increases the tendency toward abdominal fat (Cohen 1999, Tishova and Kalinchenko 2009). Sex Hormone-Binding Globulin (SHBG): Most testosterone circulating in the bloodstream is bound to either sex hormone-binding globulin (SHBG) (60%) or albumin (38%). Only a small fraction (2%) is unbound, or “free”. (Morales et al 2010). Testosterone binds more tightly to SHBG than to albumin (Henry et al 2002). Consequently, only albumin-bound testosterone and free testosterone constitute the bioavailable forms of testosterone, which are accessible to target tissues and carry out the actions of the essential hormone (Morales et al 2010). Thus the bioavailability of testosterone is influenced by the level of SHBG. Ageing men experience both an increase in aromatase activity and an elevation in SHBG production. The net result is an increase in the ratio of estrogen to testosterone and a decrease in total and free testosterone levels (Lapauw et al 2008). As will be discussed below, it is crucial that this skewed ratio be balanced. Liver Function: The liver is responsible for removing excess estrogen and SHBG, and any decrease in liver function could exacerbate hormonal imbalances and compromise healthy testosterone levels. Thus it is important that aging men also strive for optimal liver function.
Effects of Age-Related Decline in Testosterone Levels and Testosterone TherapyThe exact cause of the age-related reduction in testosterone levels is not known; it is probably the result of a combination of factors, including:
- Increasing body fat (especially belly fat, and therefore increasing aromatase activity)
- Oxidative damage to tissues responsible for the production of testosterone
- Reduction in testicular testosterone synthesis
- Declining levels of precursor molecules, such as DHEA
- Nutritional status and liver function
The Importance of Hormone TestingMillions of aging men have the dual conditions of low testosterone and high cholesterol. Conventional physicians prescribe cholesterol-lowering drugs to reduce cholesterol, when, in fact, the age-related rise in cholesterol might simply be the body’s way of increasing hormone levels by supplying the raw materials necessary to make hormones (Dzugan et al 2002). Researchers at Life Extension have successfully treated high cholesterol levels through a program of bioidentical hormone replacement therapy. Life Extension believes that comprehensive tests, along with a careful physical examination, are essential in detecting hormonal imbalances in aging men. The so-called “normal” levels of testosterone in older men reflect population averages. Life Extension believes that most aging men would prefer not to accept the loss of youthful vigor as normal. Instead, we suggest that a more valid optimal level for all men would be in the upper one-third of the reference range used for men aged 21 to 49 years, and that any supplementation should aim to restore hormone levels to that range. The current Life Extension optimal level of free testosterone is 20-25pg/mL. When measuring testosterone levels, it is critical to determine the levels of both free and total testosterone to understand the cause of any observed symptoms of deficiency (Khosla et al 2008). Because of difficulties with equipment standardization and inter-laboratory variability, it is recommended that physicians consistently use the same local laboratories and gain familiarity with the accuracy, precision and definition of normal values for the assays offered in their communities (Morales et al 2010). It is also important to remember that blood levels of both free and total testosterone vary widely among individuals, making it difficult to establish a general baseline on which to prescribe a standardized treatment protocol. However, levels are quite consistent within individuals, and thus it is important that men have multiple tests over time to determine trends and individual thresholds for treatment. Finally, during the initial testing, it is also imperative to test estrogen levels. Many of the unwanted effects of male hormone imbalance are actually caused by an elevated estrogen level relative to low testosterone levels (the estrogen/testosterone ratio). The Life Extension optimal level of estrogen (measured as estradiol) for ageing men is 20-30pg/mL.
Estrogen Balance is Critical to Aging MenA study published in the Journal of the American Medical Association (JAMA) measured blood estradiol in 501 men with chronic heart failure. Compared to men in the balanced estrogen quintile, men in the highest quintile (serum estradiol levels of 37.40 pg/mL or greater) were significantly (133%) more likely to die. Those in the lowest estradiol quintile (serum estradiol levels under 12.90 pg/mL) had a 317% increased death rate compared to the balanced group. The men in the balanced quintile—with the fewest deaths—had serum estradiol levels between 21.80 and 30.11 pg/mL (Ewa et al 2009). This is the ideal range that Life Extension has long recommended male customers to strive for. An epidemic problem that we at Life Extension observe in aging male customers is insufficient free testosterone, i.e., less than 20 – 25 pg/mL of serum. When accompanied by excess estradiol (over 30 pg/mL of serum), this can signal excess aromatase enzyme activity.
Testosterone Replacement TherapiesOptimal testosterone treatment usually requires a physician’s prescription. Integrative physicians typically prescribe bioidentical testosterone creams (available from compounding pharmacies). Conventional physicians are more likely to prescribe prepackaged, testosterone patches and/or gels from pharmaceutical companies that have sought FDA approval for the mass commercialization of their products. All forms of bioidentical testosterone have the same molecular structure and will increase free and total testosterone in the blood. The major difference is that prepackaged versions could cost up to 10 times more per dose than compounded versions. Furthermore, prepackaged testosterone gels are sold only in a limited number of doses, whereas compounded testosterone can be formulated at virtually any dose the physician feels is clinically necessary and useful.
Using Hormone Replacement WiselyIf a man opts for testosterone therapy (available orally or as an injection, subcutaneous implant, topical cream, gel, or skin patch), he should keep several facts and precautions in mind (Schaeffer et al 2004, Cunningham and Toma 2010):
- Hormone replacement should not be initiated without comprehensive testing.
- The patterns and trends over time of multiple hormone levels, (for instance free testosterone, total testosterone, and estrogen), determine the specific hormone replacements required.
- It may not be safe to use large amounts of testosterone in any form without also using aromatase-inhibiting supplements or medications.
- Because of the risk of worsening prostate cancer, careful screening, including a digital rectal examination and prostate specific antigen (PSA) screening, must be done before starting any hormone replacement program. However, recent research indicates that low endogenous testosterone levels may present a greater risk for prostate cancer than higher levels (Morgantaler 2006, Rodman et al 2008). If a man already has prostate cancer, however, testosterone replacement should be delayed until the underlying cancer is eradicated.
- A man contemplating hormone replacement, whether through a prescription or supplements, should work closely with a qualified physician to plan a rational treatment approach that includes continued monitoring and screening.
- There is no “one size fits all” treatment. Individuals vary, and hormone replacement can be a simple or complex process and often requires careful attention to signs and symptoms, as well as laboratory testing.