Subclinical Hypothyroidism and Testosterone Deficiency

Researchers writing in the International Journal of Andrology say that there is “a direct association between subclinical hypothyroidism and hypoandrogenaemia. Testosterone deficiency and its symptoms should be kept in view while managing subclinical hypothyroidism in male patients.”

Kumar A, Chaturvedi PK, Mohanty BP. Hypoandrogenaemia is associated with subclinical hypothyroidism in men. Int J Androl. 2006 Jul 24

From the article abstract:
“Hypothyroidism has been shown to be associated with a reduction in serum testosterone level in males. This reduction in testosterone is reversible by thyroxine replacement therapy. However, to the best of our knowledge, it is not yet known, whether a similar reduction in serum testosterone level is observed in subclinically hypothyroid males [thyroid-stimulating hormone (TSH) < 10 mIU/L] in whom the benefits of thyroxine replacement therapy are still controversial.

Our goal was to investigate the putative connections between subclinical hypothyroidism and the circulating levels of gonadotrophins and gonadal steroids in males (ranging from 20 to 54 years).

The serum samples from patients showing normal euthyroid and subclinical hypothyroid profiles (TSH < 10 mIU/L) were further analysed for the levels of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, sex hormone-binding globulin, progesterone and oestradiol.

Subclinical hypothyroidism was associated with a decrease in the levels of serum testosterone and its precursor progesterone. The data suggest that serum testosterone declines because of the non-availability of its precursor progesterone.

The level of oestradiol was similar in both the groups, suggesting a greater conversion rate of testosterone to oestradiol in subclinically hypothyroid males, in order to maintain the oestradiol levels.

Prolactin levels were slightly but significantly increased in subclinical hypothyroidism. To the best of our information this is a novel report, which shows a direct association between subclinical hypothyroidism and hypoandrogenaemia. Testosterone deficiency and its symptoms should be kept in view while managing subclinical hypothyroidism in male patients. Further studies are needed in order to reveal the physiological and molecular mechanisms leading to hypoandrogenaemia in subclinical hypothyroidism (TSH < 10 mIU/L).

Low Testosterone Levels and Mortality

Researchers writing in the Annals of Internal Medicine examined “whether low testosterone levels are a risk factor for mortality in male veterans.”

Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans.
Arch Intern Med. 2006 Aug 14-28;166(15):1660-5.

BACKGROUND: Low serum testosterone is a common condition in aging associated with decreased muscle mass and insulin resistance. This study evaluated whether low testosterone levels are a risk factor for mortality in male veterans.

METHODS: We used a clinical database to identify men older than 40 years with repeated testosterone levels obtained from October 1, 1994, to December 31, 1999, and without diagnosed prostate cancer. A low testosterone level was a total testosterone level of less than 250 ng/dL (<8.7 nmol/L) or a free testosterone level of less than 0.75 ng/dL (<0.03 nmol/L). Men were classified as having a low testosterone level (166 [19.3%]), an equivocal testosterone level (equal number of low and normal levels) (240 [28.0%]), or a normal testosterone level (452 [52.7%]). The risk for all-cause mortality was estimated using Cox proportional hazards regression models, adjusting for demographic and clinical covariates over a follow-up of up to 8 years. RESULTS: Mortality in men with normal testosterone levels was 20.1% (95% confidence interval [CI], 16.2%-24.1%) vs 24.6% (95% CI, 19.2%-30.0%) in men with equivocal testosterone levels and 34.9% (95% CI, 28.5%-41.4%) in men with low testosterone levels. After adjusting for age, medical morbidity, and other clinical covariates, low testosterone levels continued to be associated with increased mortality (hazard ratio, 1.88; 95% CI, 1.34-2.63; P<.001) while equivocal testosterone levels were not significantly different from normal testosterone levels (hazard ratio, 1.38; 95% CI, 0.99%-1.92%; P=.06). In a sensitivity analysis, men who died within the first year (50 [5.8%]) were excluded to minimize the effect of acute illness, and low testosterone levels continued to be associated with elevated mortality.

CONCLUSIONS: Low testosterone levels were associated with increased mortality in male veterans. Further prospective studies are needed to examine the association between low testosterone levels and mortality.

Low Testosterone Levels are Associated with Coronary Artery Disease

Researchers say that low testosterone levels are associated with coronary artery disease in male patients with angina.
Rosano GM, Sheiban I, Massaro R, Pagnotta P, Marazzi G, Vitale C, Mercuro G, Volterrani M, Aversa A, Fini M. Low testosterone levels are associated with coronary artery disease in male patients with angina.Int J Impot Res. 2006 Aug 31

From the study abstract
Historically, high androgen levels have been linked with an increased risk for coronary artery disease (CAD.) However, more recent data suggest that low androgen levels are associated with adverse cardiovascular risk factors, including an atherogenic lipid profile, obesity and insulin resistance.

The aim of the present study was to evaluate the relationship between plasma sex hormone levels and presence and degree of CAD in patients undergoing coronary angiography and in matched controls.

We evaluated 129 consecutive male patients (mean age 58+/-4 years, range 43-72 years) referred for diagnostic coronary angiography because of symptoms suggestive of CAD, but without acute coronary syndromes or prior diagnosis of hypogonadism. Patients were matched with healthy volunteers. Out of 129 patients, 119 had proven CAD; in particular, 32 of them had one, 63 had two and 24 had three vessel disease, respectively. Patients had significantly lower levels of testosterone than controls (9.8+/-6.5 and 13.5+/-5.4 nmol/l, P<0.01) and higher levels of gonadotrophin (12.0+/-1.5 vs 6.6+/-1.9 IU/l and 7.9+/-2.1 vs 4.4+/-1.4, P<0.01 for follicle-stimulating hormone and luteinizing hormone, respectively). Also, both bioavailable testosterone and plasma oestradiol levels were lower in patients as compared to controls (0.84+/-0.45 vs 1.19+/-0.74 nmol/l, P<0.01 and 10.7+/-1.4 vs 13.3+/-3.5 pg/ml, P<0.05). Hormone levels were compared in cases with one, two or three vessel disease showing significant differences associated with increasing severity of coronary disease. An inverse relationship between the degree of CAD and plasma testosterone levels was found (r=-0.52, P<0.01).

In conclusion, patients with CAD have lower testosterone and oestradiol levels than healthy controls. These changes are inversely correlated to the degree of CAD, suggesting that low plasma testosterone may be involved with the increased risk of CAD in men.

Testosterone and Prostate Cancer: An Historical Perspective on a Modern Myth

Morgentaler A.

Eur Urol. 2006 Jul 26

CONCLUSIONS: This historical perspective reveals that there is not now-nor has there ever been-a scientific basis for the belief that T causes pCA to grow. Discarding this modern myth will allow exploration of alternative hypotheses regarding the relationship of T and pCA that may be clinically and scientifically rewarding.

Read More
Testosterone replacement therapy and the risk of prostate cancer
The article says “The belief that testosterone increases the risk of prostate cancer is so widely accepted that study after study that tries to show it and can’t keeps getting repeated over and over,” says Dr. Abraham Morgentaler, a Boston urologist and author of the 2004 review. “People don’t believe it.”

Estradiol, Testosterone, and Hip Fractures in Men

Researchers writing in The American Journal of Medicine say “Men with low estradiol levels are at an increased risk for future hip fracture. Men with both low estradiol and low testosterone levels seem to be at greatest risk for hip fracture.”

Estradiol, Testosterone, and Hip Fractures in Men.
Shreyasee A, Zhang Y, Felson DT, Sawin CT, Hannan MT, Wilson PWF, Kiel DP. Estradiol, Testosterone, and the Risk for Hip Fractures in Elderly Men from the Framingham Study. The American Journal of Medicine Volume 119, Issue 5 , May 2006, Pages 426-433

Testosterone, Alzheimer’s, Mood and Quality of Life

Effects of Testosterone on Cognition and Mood in Male Patients With Mild Alzheimer Disease and Healthy Elderly Men. Lu PH, Masterman DA, Mulnard R, Cotman C, Miller B, Yaffe K, Reback E, Porter V, Swerdloff R, Cummings JL. Arch Neurol. 2005 Dec 12

From the study abstract: “There is a compelling need for therapies that prevent, defer the onset, slow the progression, or improve the symptoms of Alzheimer disease (AD).

OBJECTIVE: To evaluate the effects of testosterone therapy on cognition, neuropsychiatric symptoms, and quality of life in male patients with mild AD and healthy elderly men.

RESULTS: For the patients with AD, the testosterone-treated group had significantly greater improvements in the scores on the caregiver version of the quality-of-life scale. No significant treatment group differences were detected in the cognitive scores at end of study, although numerically greater improvement or less decline on measures of visuospatial functions was demonstrated with testosterone treatment compared with placebo.

In the healthy control group, a nonsignificant trend toward greater improvement in self-rated quality of life was observed in the testosterone-treated group compared with placebo treatment. No difference between the treatment groups was detected in the remaining outcome measures. Testosterone treatment was well tolerated with few adverse effects relative to placebo.”

CONCLUSIONS: Results suggest that testosterone replacement therapy improved overall quality of life in patients with AD. Testosterone had minimal effects on cognition.

Read the abstract

Link Between Testosterone and Prostate Cancer

March 14, 2006
Testosterone Replacement Therapy and the Risk of Prostate Cancer. Is there a link?

Writing in the Canadian Journal of Urology, Researcher Abraham Morgentaler of the Division of Urology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, says that “there is an absence of scientific data supporting the concept that higher testosterone levels are associated with an increased risk of prostate cancer.”

Specifically, no increased risk of prostate cancer was noted in 1) clinical trials of testosterone supplementation, 2) longitudinal population-based studies, or 3) in a high-risk population of hypogonadal men receiving testosterone treatment. Moreover, hypogonadal men have a substantial rate of biopsy-detectable prostate cancer, suggesting that low testosterone has no protective effect against development of prostate cancer.

These results argue against an increased risk of prostate cancer with testosterone replacement therapy.

Morgentaler A.Testosterone replacement therapy and prostate risks: where’s the beef? Can J Urol. 2006 Feb;13 Suppl 1:40-3. Read the abstract

From our December 6, 2005 Newsletter
An article by Susan Brink of the Los Angeles Times recently appeared in newspapers around the country discussing the link between testosterone and prostate cancer.

The article says “The belief that testosterone increases the risk of prostate cancer is so widely accepted that study after study that tries to show it and can’t keeps getting repeated over and over,” says Dr. Abraham Morgentaler, a Boston urologist and author of the 2004 review. “People don’t believe it.”

Here is a press release from the Harvard Medical School.

“Boston–January 2004, Harvard Medical School affiliate Beth Israel Deaconess Medical Center–A retrospective analysis by researchers at Beth Israel Deaconess Medical Center published in The New England Journal of Medicine found no causal relationship between testosterone replacement and prostate cancer or heart disease risk. The comprehensive review of 72 studies, addresses the current controversy about testosterone replacement therapy and its potential health risks to men.”

Low Testosterone and the Pro-Inflammatory State in Aging Men

Researchers writing in the Journal of Endocrinological Investigation “suggest that a close relationship exists between the development of a pro-inflammatory state and the decline in Testosterone levels” and that “observational and interventional studies suggest that Testosterone supplementation reduces inflammatory markers in both young and old hypogonadal men. ”

Maggio M, Basaria S, Ceda GP, Ble A, Ling SM, Bandinelli S, Valenti G, Ferrucci L. The relationship between testosterone and molecular markers of inflammation in older men. J Endocrinol Invest. 2005;28(11 Suppl 2):116-9.

Other Links
Testosterone for Men
Testosterone and Bone Loss in Elderly Men
Older Men and Testosterone
More Testosterone Research Concerning Older Men
Testosterone replacement therapy and the risk of prostate cancer
Testosterone, Estrogen and Bone Loss
Risk factors for testosterone loss in aging men

The medicinal value of testicles have been documented in the Bible, the writings of the ancient Egyptians and from India. Indeed, nearly every ancient culture believed that the testicles held some form of masculine power. From our Age Management Booklet…read more

More Body Mass…Diminished Testosterone

Osuna C JA, Gomez-Perez R, Arata-Bellabarba G, Villaroel V. Relationship between bmi, total testosterone, sex hormone-binding-globulin, leptin, insulin and insulin resistance in obese men. Arch Androl. 2006 Sep-Oct;52(5):355-61

From the study abstract: The objective of this work was to evaluate the relationship between sex steroid hormones, sex hormone-binding-globulin, leptin, insulin and insulin resistance in obese men. Anthropometrical indexes, total testosterone, free testosterone, estradiol, sex hormone-binding-globulin (SHBG), glucemia, insulin and leptin were measured in 77 men, with ages between 20 and 60 years.

According to their body mass index (BMI), subjects were grouped into three categories: normal body weight, overweight and obese group.

Total testosterone and SHBG concentrations were lower in the obese group compared with normal and overweight subjects.

The mean insulin concentration was significantly higher in the obese group compared with the other groups.

Our results shows that in a sample of men, total testosterone and SHBG concentrations proportionally diminished with both the increase of BMI and insulin resistance index.

Androgen Deficiency, Metabolic Syndrome and Non-Obese Men

Researchers writing in The Journal of Clinical Endocrinology and Metabolism report that “Low SHBG, total testosterone, or AD (Androgen Deficiency) may be early markers of MetS (Metabolic Syndrome) in nonobese men, providing a warning sign in men otherwise considered at lower risk of developing MetS and subsequent diabetes or cardiovascular disease.”

From the study: “Low serum SHBG, low total testosterone, and clinical AD are associated with increased risk of developing MetS over time, particularly in non-overweight middle-aged men.”

You can read the abstract here and link to the a free copy of the entire study from there.
Kupelian V, Page ST, Araujo AB, Bremner WJ, McKinlay JB. Low SHBG, Total Testosterone, and Symptomatic Androgen with Development of the Metabolic Syndrome. J Clin Endocrin Metab. January 4, 2006

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