Читать книгу Anti-Aging Therapeutics Volume XV - A4M American Academy - Страница 15

Testosterone is the main hormone produced in the testicles and secreted by the testes. Testosterone deficiency has pleiotropic deleterious effects. There is increased cardiovascular system dysfunction, which can lead to the increased incidence of AMI’s and strokes. Citing separately published data finding that: “serum testosterone levels were proved to be an independent negative predictor for developing arterial stiffness, assessed from the peak

systolic and end diastolic diameters of the common carotid artery and simultaneous brachial artery blood pressure,” Kelly and Jones⁶² submit that: “testosterone has demonstrated anti-inflammatory effects clinically and [testosterone replacement therapy] can improve atherosclerosis assessed non-invasively in hypogonadal men and in animal studies.”

Testosterone²² optimization is anti-inflammatory. Testosterone prevents cytokine production and initiates the acute phase response, which elevates C-reactive protein, serum amyloid A and fibrinogen. Testosterone also prevents the formation of the adhesion molecules vascular cell adhesive molecule (VCAM) and intercellular adhesive molecule, (CD 54/ICAM), which are necessary components of the process of atherosclerosis. Thus, testosterone replacement is a very powerful anti-inflammatory treatment that can help to prevent atherosclerosis. Testosterone has also been shown to be of benefit in thetreatment of chronic heart failure. Pugh et al.⁵³ found that testosterone increases cardiac output, decreases left ventricular load, and has no adverse cardiovascular effects. Malkin et al.⁵⁴ show that testosterone replacement moderates inflammatory cytokines and improves heart failure outcomes. Turhan et al.⁵⁵ found that men with low free testosterone levels have greater than 3 times the risk for the development of coronary artery disease.

There²² is a common misconception that testosterone has adverse cardiovascular effects. However, the opposite has been shown with current research. The lower the free testosterone level the more likely coronary artery disease will be present. Testosterone replacement therapy (TRT) improves ST depression and dilates coronary arteries. TRT also may improve lipids and low testosterone is associated with dyslipidemia. English et al. found that low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina. Rosano et al.⁵⁶ found that "Short-term administration of testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary artery disease.” The same researchers also concluded that intracoronary testosterone has direct dilating effects on the coronary arteries. Finally, Hak et al.⁵⁷ found that low levels of endogenous androgens increase the risk of atherosclerosis in elderly men.

Testosterone²² can be a very powerful tool for the control of insulin resistance. Replacement doses decrease insulin resistance. Low levels of testosterone play a role in the development of type 2 diabetes. Low testosterone is associated with metabolic syndrome, hypertension, type II diabetes, fibromyalgia, and coronary artery disease. Boyanov et al.⁵⁸ studied the effect of testosterone supplementation in men with type 2 diabetes, visceral obesity, and partial androgen deficiency. Subjects received testosterone undecanoate, and the results reflect that supplementary testosterone reduced hemoglobin A1C levels by 17.3%, led to a decrease in visceral obesity, and improved symptoms of androgen deficiency including erectile dysfunction. Observing that: “There is strong evidence that a low testosterone level and clinical hypogonadism have a high prevalence n men with metabolic syndrome and/or type 2 diabetes,” Muraleedharan and Jones⁵⁹ conclude that: “Testosterone deficiency is a risk factor in itself for the subsequent development of the metabolic syndrome and type 2 diabetes.”

Testosterone²² is the major predictor of skeletal mass, and it is synergistic with growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Bhasin et al.⁶⁰ show that testosterone can improve strength even without exercise, but there is a marked improvement if testosterone is taken in combination with exercise. Declining testosterone levels are associated with accelerated osteoporosis, decreased muscle mass, and anemia – i.e., frailty.

Numerous studies have documented testosterone’s positive effects on body composition. Mudali and Dobs⁶¹ write: “Studies in hypogonadal men have shown that testosterone replacement is effective in increasing muscle mass and strength and decreasing fat mass…Current evidence suggests that testosterone replacement may be effective in reversing age-dependent body composition changes and associated morbidity.” LeBlanc et al⁶² analyzed data collected on 1,183 men, ages 65 years and older, following the subjects for 4.5 years. Body composition was measured using dual energy x-ray absorptiometry (DXA) scans and physical performance was measured through a series of exercises that assessed grip strength, lower extremity power, walking speed and the ability to rise from a chair without the use of arms. Results showed that higher levels of testosterone were associated with reduced loss of lean muscle mass in older men, especially in those who were losing weight. In these men, higher testosterone levels were also associated with less loss of lower body strength. The study authors concluded: “Higher endogenous testosterone is associated with reduced loss of lean mass and lower extremity function in older men losing weight. Endogenous testosterone may contribute to healthy aging.” Kovacheva et al⁶³ report that testosterone supplementation reverses sarcopenia in aging via regulation of myostatin and “multiple signal transduction pathways in sarcopenia,” concluding that: ‘Testosterone reverses sarcopenia through stimulation of cellular metabolism and survival pathway together with inhibition of death pathway.”

Testosterone²² levels correlate with cognitive function, and TRT can improve cognitive function. Moffat et al.⁶⁴ found that serum free testosterone concentration can be used to predict memory performance and cognitive status in elderly men. Gouras et al⁶⁵ showed that testosterone replacement therapy prevents the production of beta amyloid precursor protein in men, which suggests that testosterone replacement may play a role in the prevention of Alzheimer's disease. A pilot study by Tan⁶⁶ on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease revealed that mental status of those given testosterone replacement therapy improved over one year, whereas the mental status of those given a placebo declined. Janowsky et al⁶⁷ found that increasing testosterone to 150% of baseline levels in older men resulted in a significant enhancement of spatial cognition. A review of testosterone and cognition in elderly men, Holland et al⁶⁸ concluded that: "Results from cell culture and animal studies provide convincing evidence that testosterone could have protective effects on brain function. Testosterone levels are lower in Alzheimer's disease cases compared to controls, and some studies have suggested that low free testosterone (FT) may precede Alzheimer's disease onset...Positive associations have been found between testosterone levels and global cognition, memory, executive functions, and spatial performance in observational studies."

Studies have shown that men who have their testosterone levels restored with TRT are less likely to suffer from depression, are less moody, more sociable, and have more energy. O’Connor et al⁶⁹ investigated the effects of TRT on self- and partner-reported aggression and mood. Eight hypogonadal men received 200 mg intramuscular testosterone biweekly for 8 weeks. Results showed that TRT led to significant reductions in negative mood, tension, anger, and fatigue. Aydogan et al⁷⁰ assessed the relationship with testosterone levels and psychological symptoms in young male patients with congenital hypogonadotropic hypogonadism (CHH). 39 young male patients with CHH and 40 age-matched healthy males were enrolled in the study. Results showed that hypogonadal participants had more severe symptoms of sexual dysfunction, anxiety, depression, and worse quality of life. However, 6 months of TRT led to improvements in anxiety and depression scores and the life qualities of participants. TRT also improves sexual function. Khera et al⁷¹ investigated if 12-months of treatment with a testosterone gel improved sexual function in hypogonadal men, as measured by the Brief Male Sexual Function Inventory (BMSFI). Results showed that the mean total BMSFI score significantly increased from baseline at 12 months (27.4 ± 10.3 to 33.8 ± 9.8, P < 0.001) and at each visit in all domains (sex drive/libido, erectile function, ejaculatory function, level of bother). Regression analysis indicated that increased total BMSFI score was significantly associated with increased total testosterone levels at 6 months. The authors concluded: "In hypogonadal patients, 12-month administration of topical testosterone gel resulted in increased total testosterone and free testosterone levels and significantly improved sexual function."

A Cochrane systematic study reviewed the benefits of testosterone for peri- and postmenopausal women. The authors concluded that “there is evidence that adding testosterone to hormone therapy has a beneficial effect on sexual function in postmenopausal women. There was a reduction in HDL cholesterol associated with the addition of testosterone to the hormone therapy regimens. Due to lack of targeted research, it is difficult to estimate the effect of testosterone on sexual function in association with any individual hormone treatment regimen.”⁷²

Rhoden²² et al.⁷³ point out that benign prostatic hyperplasia (BPH) symptoms are not exacerbated with testosterone supplementation. Cooper et al.⁷⁴ studied the effect of exogenous testosterone on prostate volume, serum and semen prostate specific antigen (PSA) levels in healthy young men. Participants were given testosterone intramuscularly at doses of 100, 250, or 500 mg a week. Serum testosterone increased, and there was no change in prostate volume or serum and semen PSA. Morales⁷⁵ and Prehn⁷⁶ both concluded that there is no evidence to suggest that exogenous androgens promote the development of prostate cancer. Morley⁷⁷ states that “There is no clinical evidence that the risk of either prostate cancer or BPH increases with testosterone replacement therapy.” A collaborative analysis published in the Journal of the National Cancer Institute in 2008 found that there was no association between the risk of prostate cancer and any hormone measured, including testosterone, DHT, estradiol and others. Gould et al.⁷⁸ review of 15 studies of testosterone replacement, up to 15 years in duration, showed no increase of prostate cancer risk. Agarwal⁷⁹ and Sarosdy⁸⁰ found that testosterone treatment studies of patients with prostate cancer after radical prostatectomy and brachytherapy have shown no recurrences or significant increases of PSA. Morgantaler’s⁸¹ study reported dramatic evidence on the safety profile of TRT: 13 testosterone deficient men with biopsy proven prostate cancer were treated with TRT. After 2.5 years repeat biopsies were done and no cancer was found in 54%, there was also no local progression or metastasis found.