Subclinical Hypothyroidism and Depression

Researchers writing in the Archives of Gerontology and Geriatrics say that “subclinical hypothyroidism increases the risk for depression and emphasize the importance of thyroid screening tests in the elderly.”

Study abstract
Chueire VB, Romaldini JH, Ward LS. Subclinical hypothyroidism increases the risk for depression in the elderly. Arch Gerontol Geriatr. 2007 Jan-Feb;44(1):21-8. Epub 2006 May 5.

In order to determine if subclinical hypothyroidism is a risk factor for depression in the elderly, a total of 323 individuals over 60 years old were interviewed using the Structured Clinical Interview for Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) for mood disturbances.

Patients were divided into Group I: 252 patients (184 females, 68 males; median age: 67 years, range: 60-89 years) with elevated serum thyrotropin (TSH) levels and Group II: 71 patients (45 females, 26 males; median age: 67 years, range: 60-92 years) with diagnosis of depression. Serum TSH and free thyroxine (fT4) were measured by sensitive assays. Thyroid antibodies were determined by IRMA. Depression was observed in 24 (9.5%)

Group I patients and was frequent in subclinical hypothyroidism patients (14/24 = 58.3%). On the other hand, elevated TSH levels were found in 22 (30.9%) Group II patients.

Depression was observed more frequently among individuals with subclinical (74/149 = 49.7%) hypothyroidism than among individuals with overt hypothyroidism (21/125 = 16.8%) (p < 0.001). Indeed, subclinical hypothyroidism increased the risk for a patient to present depression more than four times (OR = 4.886; 95% confidence interval = 2.768-8.627).

Our results demonstrate that subclinical hypothyroidism increases the risk for depression and emphasize the importance of thyroid screening tests in the elderly.

Pregnenolone Research

Sleep and Memory

George O, Vallee M, Le Moal M, Mayo W. Neurosteroids and cholinergic systems: implications for sleep and cognitive processes and potential role of age-related changes Neurosteroids and cholinergic systems: implications for sleep and cognitive processes and potential role of age-related changes. Psychopharmacology (Berl). 2006 Jan 17;:1-12

Rationale: The neurosteroids pregnenolone sulfate (PREGS), dehydroepiandrosterone sulfate (DHEAS) and allopregnanolone (3alpha,5alpha THPROG) have been implicated as powerful modulators of memory processes and sleep states in young and aged subjects with memory impairment. As these processes depend on the integrity of cholinergic systems, a specific effect of neurosteroids on these systems may account for their effects on sleep and memory.

Objective: To review the evidence for a specific and differential effect of neurosteroids on cholinergic systems.

Conclusions: The specific modulation of basal forebrain and brainstem cholinergic systems by neurosteroids may account for the effects of these compounds on sleep and memory processes. To improve our understanding of the role of neurosteroids in cholinergic systems during normal and pathological aging, we need to determine whether there is specific regionalization of neurosteroids, and we need to investigate the relationship between neurosteroid concentrations in cholinergic nuclei and age-related sleep and memory impairments.

Alzheimer’s
Neurosteroid quantification in human brain regions: comparison between Alzheimer’s and nondemented patients.

Weill-Engerer S, David JP, Sazdovitch V, Liere P, Eychenne B, Pianos A, Schumacher M, Delacourte A, Baulieu EE, Akwa Y.Neurosteroid quantification in human brain regions: comparison between Alzheimer’s and nondemented patients.J Clin Endocrinol Metab. 2002 Nov;87(11):5138-43

Abstract: “…To investigate the physiopathological significance of neurosteroids in Alzheimer’s disease (AD), we compared the concentrations of pregnenolone, pregnenolone sulfate (PREGS), dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), progesterone, and allopregnanolone…in individual brain regions of AD patients and aged nondemented controls, including hippocampus, amygdala, frontal cortex, striatum, hypothalamus, and cerebellum.

A general trend toward decreased levels of all steroids was observed in all AD patients’ brain regions compared with controls: PREGS and DHEAS were significantly lower in the striatum and cerebellum, and DHEAS was also significantly reduced in the hypothalamus. A significant negative correlation was found between the levels of cortical beta-amyloid peptides and those of PREGS in the striatum and cerebellum and between the levels of phosphorylated tau proteins and DHEAS in the hypothalamus. This study provides reference values for steroid concentrations determined by gas chromatography-mass spectrometry in various regions of the aged human brain. High levels of key proteins implicated in the formation of plaques and neurofibrillary tangles were correlated with decreased brain levels of PREGS and DHEAS, suggesting a possible neuroprotective role of these neurosteroids in AD.”

Pregnenolone main page

Pregnenolone

Pregnenolone is a steroid hormone synthesized from cholesterol mainly by the adrenal glands and in small part by our nervous system.

What does it do?
There is speculation as to the main role of pregnenolone in the body. Most researchers are now in agreement that the primary role of pregnenolone is as the precursor (the building block) of our other hormones including the estrogens, progesterone, testosterone and DHEA.

DHEA is considered the “daughter” hormone of pregnenolone. Indeed pregneolone is considered by some to be the “mother of all steroid hormones.”

It has been suggested by human and animal studies that pregnenolone may assist:
-Memory enhancement
-Feelings of well being
-Intelligence by increasing ability to acquire knowledge
-Reduction of physical and mental effects of stress
-Mood improvement
-Energy improvement
-Reduction of PMS and menopausal symptoms
-Better sleep and deeper sleep
-Reduction of wrinkles through skin hydration
-As an anti-inflammatory, and with benefits for rheumatoid arthritis

Pregnenolone supplementation
As do our other hormones, pregnenolone levels decline with age. In our seventies, many produce up to 60% less pregnenolone than we did in our thirties. Many physicians and scientists believe that replacement of pregnenolone to those levels of our thirties can help with the symptoms regularly attributed to aging.

Another aspect of pregnenolone that researchers find intriguing is that pregnenolone levels may regulate the levels of our other hormones. In other words, supplementation of pregnenolone may positively impact decreased levels of our other hormones and restore them to more optimal levels.

There is a negative. If increasing pregnenolone levels increases the body’s own ability to make hormones, such as DHEA, then concurrent supplementation can theoretically raise other hormone levels too high. This is yet another reason why self-administering any hormone is not advisable and should be done only after levels are drawn and analyzed by an age management specialist.

Pregnenolone Research

Intimacy, Urinary, and Depressive Problems In Women Who Have Partners With E.D.

Researchers writing in the medical journal World Journal of Urology say that FSD disorders, urinary symptoms and depressive symptoms are common in partners of men with ED.

From the study abstract
Shabsigh R, Anastasiades A, Cooper KL, Rutman MP. Female sexual dysfunction, voiding symptoms and depression: common findings in partners of men with erectile dysfunction. World J Urol. 2006 Nov 3

The researchers sought to “investigate the prevalence of female sexual dysfunction (FSD), urinary symptoms, and depressive symptoms in female partners of men presenting with erectile dysfunction (ED).”

Through a survey 73 women with male patients presenting with ED were surveyed using a questionnaire at their counterpart’s visit. Fifty of the women filled out the questionnaire sufficiently to be studied.

Of the 50 women, the average age was 44.8 years and 38 of the women reported being sexually active

The women reported the following sexual dysfunctions:

• anxiety/inhibition (26%)
• hypoactive desire (20%)
• arousal/lubrication difficulty (30%)
• orgasmic difficulty (24%)
• dyspareunia* (18%)
• incontinence during intercourse (8%)
• sexual dissatisfaction (34%)



In other questions the women reported:
Forty-one women (82%) rated sexual activity as an important part of their lives.
Urinary symptoms of frequency and urgency were reported by 18/50 (36%).
Depressive symptoms were present in 22/50 (44%).

The researchers noted that: “FSD disorders, urinary symptoms and depressive symptoms are common in partners of men with erectile dysfunction.”

*Note added: Painful intercourse

In the News

 
Walking off Postmenopausal decreases in bone mineral density, aerobic fitness, muscle strength, and balance. Researchers writing in the medical journal Physical Therapy say that “Menopause may induce a phase of rapid decreases in bone mineral density, aerobic fitness, muscle strength, and balance, especially in sedentary women. The purpose of this study was to examine the effects and feasibility of an exercise program of 1 or 2 bouts of walking and resistance training on lower-extremity muscle strength (the force-generating capacity of muscle), balance, and walking performance in women who recently went through menopause.”
Read more

 

 

From our last issue…
Men and Testosterone More Body Mass…Diminished Testosterone
Researchers writing in the medical journal Archives of Andrology say total testosterone and SHBG concentrations proportionally diminished with both the increase of BMI (body mass index) and insulin resistance index. Read more

 

 

Intimate Activity and Level of Satisfaction in Middle Aged and Older Women
Researchers writing in the medical journal Obstetrics & Gynecology looked at women aged 40-69 for their levels of intimate activity and satisfaction, see what they found.

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Testosterone, Diabetes, Metabolic Syndrome

Recent research in the International Journal of Impotence Research say testosterone may have a protective role in the development of metabolic syndrome and subsequent diabetes mellitus and cardiovascular disease in aging men. However, clinical trials are needed to confirm this assumption.

Svartberg J.Epidemiology: testosterone and the metabolic syndrome.Int J Impot Res. 2007 Mar-Apr;19(2):124-8.

Low levels of testosterone, hypogonadism, have several common features with the metabolic syndrome. In the Tromso Study, a population-based health survey, testosterone levels were inversely associated with anthropometrical measurements, and the lowest levels of total and free testosterone were found in men with the most pronounced central obesity.

Total testosterone was inversely associated with systolic blood pressure, and men with hypertension had lower levels of both total and free testosterone.

Furthermore, men with diabetes had lower testosterone levels compared to men without a history of diabetes, and an inverse association between testosterone levels and glycosylated hemoglobin was found. Thus, there are strong associations between low levels of testosterone and the different components of the metabolic syndrome. In addition, an independent association between low testosterone levels and the metabolic syndrome itself has recently been presented in both cross-sectional and prospective population-based studies. Thus, testosterone may have a protective role in the development of metabolic syndrome and subsequent diabetes mellitus and cardiovascular disease in aging men. However, clinical trials are needed to confirm this assumption.

Insulin Sensitivity and Men with Heart Failure

Researchers writing in the European Journal of Heart Failure say “Testosterone improves fasting insulin sensitivity in men with chronic heart failure and may also increase lean body mass, these data suggest a favourable effect of testosterone on an important metabolic component of chronic heart failure”

Malkin CJ, Jones TH, Channer KS. The effect of testosterone on insulin sensitivity in men with heart failure.European Journal of Heart Failure 2007 Jan;9(1):44-50.
Resistance to insulin occurs in chronic heart failure (CHF) and is related to prognosis.

Studies of testosterone in non-(CHF) males suggest that physiological testosterone therapy improves insulin sensitivity.

This was a single-blind placebo controlled crossover trial to determine the effect of testosterone replacement on insulin sensitivity in 13 men with moderate to severe CHF (ejection fraction 30.5+/-1.3). The primary outcome was the homeostatic model index (HOMA-IR) of fasting insulin sensitivity and secondary outcomes were body composition as measured by bioelectrical impedance and glucose tolerance to a standard 75 g oral glucose load. Analysis was performed on the delta values with the treatment effect of placebo compared with that of testosterone. At baseline HOMA-IR correlated with measures of body fat [% fat mass (rP=0.84, p=0.0001) and body mass index (rP=0.79, p=0.01)] but not with CHF severity.

Testosterone reduced HOMA-IR (-1.9+/-0.8, p=0.03) indicating improved fasting insulin sensitivity. Testosterone also increased total mass (+1.5+/-0.5 kg, p=0.008) and decreased body fat (-0.8+/-0.3%, p=0.02).

Testosterone improves fasting insulin sensitivity in men with CHF and may also increase lean body mass, these data suggest a favourable effect of testosterone on an important metabolic component of CHF.

Testosterone and the Aging Male

A published report in the medical journal Aging Male says “The wide-ranging benefits of testosterone therapy in young and old men are clear and it appears that the route of administration (intramuscular, oral, or transdermal) does not alter this fact, but future work could illustrate even more profound effects of testosterone (e.g., in reducing cardiovascular risk) that could result in its recommended use in a wider range of patients.”

Abstratct:

Kohn FM. Testosterone and body functions. Aging Male. 2006 Dec;9(4):183-8

Testosterone supplementation can help reduce many of the symptoms associated with androgen deficiency in the aging male by its effects on various parts of the body.

Bone mineral density can decrease in the hypogonadal man and this may contribute to the increased fracture rate in the elderly. Testosterone therapy can improve bone mineral density and bone architecture by increasing bone formation and decreasing bone resorption – the possible benefits on fracture rate are unknown.

Testosterone also improves body composition by reducing body fat mass and increasing lean body mass, and by increasing epidermal thickness, but its effects on muscle strength are still debated.

In patients with diabetes and androgen deficiency, testosterone supplementation appears to reduce blood glucose and this could have important implications for cardiovascular risk reduction in patients with diabetes or the metabolic syndrome.

The wide-ranging benefits of testosterone therapy in young and old men are clear and it appears that the route of administration (intramuscular, oral, or transdermal) does not alter this fact, but future work could illustrate even more profound effects of testosterone (e.g., in reducing cardiovascular risk) that could result in its recommended use in a wider range of patients.

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.

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