Re-analysis of Carlsen's work on sperm count finds consistent decline in sperm count. Swan and authors found a 1.5% decline in US men from 1934-1996 and 3% annual decline in European/Australian men over same time frame. This was a meta-analysis of 101 studies from 1934-1996. Yes, there is geographical variation, but the overall trend is one of decline.
the age trend in free T was more substantial (−1.3% per annum)
The core hormonal pattern with increasing age is suggestive of incipient primary testicular dysfunction with maintained total T and progressively blunted free T associated with higher LH.
Obesity was associated with progressively lower total and free T independent of the simultaneous decrease in SHBG.
our data highlight the fact that LH was unchanged or even lower in older men in the face of lower T in obesity, suggesting that there may be a failure at the hypothalamic-pituitary level.
a change in BMI from nonobese to obese may be equivalent to a 15 yr fall in T.
This pattern supports the hypothesis that different underlying mechanisms influence the functions of the HPT axis: age predominantly affects testicular function, whereas obesity impairs hypothalamic/pituitary function.
the effects of aging on testicular function can be moderated by increased LH compensation for many decades
obesity impairs hypothalamic/pituitary function independent of age, arguably an adaptive response for which there should be no compensatory mechanism.
the concurrent but opposite (and separate) effects of obesity and age on SHBG
SHBG was negatively associated with increasing strata of obesity
Obesity is associated with insulin resistance (28), and the increased circulating insulin inhibits hepatic SHBG synthesis
the SHBG increase with age may be related to relative IGF-I deficiency (27), although this has not been directly proven.
Obesity is associated with peripheral and central insulin resistance (30) and proinflammatory cytokine production (TNFα and IL-6) from adipocytes (31) and central nervous system endocannibinoid release (32), all of which are potential candidates for abrogating hypothalamic endocrine and downstream reproductive axis functions.
The HPA axis effect may be the result of inflammation.
The relationship between obesity and T can be bidirectional: low T may be the cause rather than consequence of obesity
chronic alcohol abuse is known to suppress LH (40), our data showed no significant association among the three hormones or SHBG and alcohol intake.
increase in total T in smokers occurs through a primary increase in SHBG with a compensatory rise in LH
the effects of obesity (BMI or waist circumference) was by far the most important determinant of variance in total T, whereas age per se was important for SHBG, LH, and free T with comorbidity and smoking being comparatively minor contributors
It is noteworthy that these predisposing lifestyle and health factors are modifiable. This implies that the apparent age-related decline in T may constitute a barometer of health and thus be potentially preventable and/or reversible.
Age induced decline in Testosterone is more associated with a decline in leydig cell function and thus elevated LH will be associated. In contrast, obesity is more of a HPA axis disruption and thus LH may be normal to low. The pulse amplitude is decrease. No change in pulse frequency is noted.
With obesity, a decline in TT and fT was independent of SHBG.
Aging is associated with a greater decrease in fT versus TT.
SHBG decreases in response to androgens, and in the presence of hypothyroidism, and insulin resistance.
Plasma SHBG levels tend to increase with increasing age
The apparent metabolic clearance rate of testosterone is decreased in elderly as compared to younger men
Testosterone circulates predominantly bound to the plasma proteins SHBG and albumin, with high and low affinity respectively
Testosterone is secreted in a pulsatile fashion
Current clinical guidelines suggest at least two measurements
In adult men, there is a well-documented diurnal variation (particularly in younger subjects) in testosterone levels, which are highest in the early morning and progressively decline throughout the day to a nadir in the evening
In older men, the diurnal variation is blunted
it is standard practice for samples to be obtained between 0800 and 1100 h.
Testosterone and DHEA decline, whereas LH, FSH, and SHBG rise
DHT remains constant despite the decline of its precursor testosterone
Longitudinal studies show an average annual decline of 1–2% total testosterone levels, with decline in free testosterone more rapid because of increases in SHBG with aging
Massachusetts Male Aging Study (MMAS) data show DHEA, DHEAS, and Ae declining at 2–3% per year
DHT showed no cross-sectional age trend
Androstanediol glucuronide (AAG) declined cross-sectionally with age in the MMAS sample, at 0.6% per year
The EMAS data show that, consistent with the longitudinal findings of MMAS (Figure 1), the core hormonal pattern with increasing age is suggestive of incipient primary testicular dysfunction with maintained total testosterone and progressively blunted free testosterone associated with higher LH
This author proves the point in the review of these two studies, that TT may remain constant in aging men, however, FT drops.
obesity impairs hypothalamic/pituitary function
Androgen deprivation in men with prostate cancer has been associated with increased insulin resistance, worse glycemic control, and a significant increase in risk of incident diabetes
Low serum testosterone is associated with the development of metabolic syndrome 116, 117 and type 2 diabetes. 118 SHBG has been inversely correlated with type 2 diabetes
Improvement in insulin sensitivity with testosterone treatment has been reported in healthy 121 and diabetic 122 adult men
In studies conducted in men with central adiposity, testosterone has been shown to inhibit lipoprotein lipase activity in abdominal adipose tissue leading to decreased triglyceride uptake in central fat depots. 123
increased estradiol and estrone levels in men associated with cognitive decline. This was distinct from age, CVD, and APOE genotype. This points to a clear association between increased aromatase activity and inflammation that contributes to cognitive decline in men.
26 year study of dogs finds declining sperm count equivalent to that in men. The decline was found to occur at a rate of 1.2% to 2.5% annually over course of study. The authors pointed to EDC's in food.
Postmenopausal cognitive decline is a common complaint. Declining Estradiol and progesterone have been implicated, in part, to this cognitive decline. This study finds that progesterone increases expression of Transthyretin, a protein that processes amyloid Beta protein. This amyloid Beta protein is associated with damage found in Alzheimer's.
Weak connection, but this study finds that Testosterone in post-menopausal women will reduce cardiovascular disease (CVD) in women. Their conclusion is based on the rise in CVD in post-menopausal women and the decline in Testosterone levels post-hysterectomy. That is the one instant where Testosterone levels do precipitously decline. Contrast this with natural menopause where Testosterone does not appear to decline as precipitously.
Statin use found to be associated with cognitive decline. The authors defined use as long-term, though 2 years of use was found to be associated with decline. interestingly, metabolic syndrome was not found to be associated with cognitive decline.
Decline in concentration, function and morphological normal sperm in young men in Paris. This was a 20 year study. There was no reduction in semen volume.
Just the abstract here. Declining estradiol production found to be associated with increased cognitive dysfunction or cognitive decline in those using aromatase inhibitor therapy. Aromatase inhibition therapy is used to block Testosterone to Estradiol production in women with ER+ breast cancer.
Untold risk of early ovary removal appears to be cognitive decline and increased risk of dementia. The earlier the age of removal, the more the increased risk of cognitive decline.
aging in men is associated with decreases in bone mineral density (BMD) (18, 19), lean body and muscle mass
strength (22, 23) and aerobic capacity (24), as well as with increases in total and abdominal body fat, low-density lipoprotein cholesterol, and/or low-density lipoprotein/high-density lipoprotein cholesterol ratios (25, 26, 27, 28), all of which also occur in nonelderly hypogonadal men
Most (1, 5, 6, 7, 8, 9), but not all (10, 11, 12), cross-sectional studies have demonstrated a decrease, with age, in total T in men
These numbers do point to an increase in ng/dl decline in Total Testosterone with increasing age (decade group)
total T, but not free T index, tended to decrease with greater BMI is consistent with prior studies showing that obesity is associated with decreases in both SHBG and total T, with an unchanged T-to-SHBG ratio
The conventional definition for T levels is statistical (values more than 2 sd below the mean), rather than functional. Such a definition does not reflect clinical realities, such as the existence of characteristic individual set points for circulating hormone levels, below which one, but not another, individual may develop metabolic changes of hormone deficiency; nor does it address the concept of reserve capacity, the possibility that persons with hormone levels 2 sd below the population mean still may have adequate hormone concentrations to meet their metabolic needs.
good explanation of problems with just using a number to define low T
both T and free T index (a calculated value related to free or bioavailable T) decreased progressively at a rate that did not vary significantly with age, from the third to the ninth decades.
contrasts with other studies showing diminished free, as well as total, T in with increasing total (48) or abdominal (49) obesity in men.
Our analysis of date-adjusted T and free T index levels, by decade, showed that relatively high numbers of older men in this generally healthy population had at least one hypogonadal value (defined as below the 2.5th percentile for young men)
The issue of how properly to define hypogonadism, or indeed any hormone deficiency, remains problematic
The decrease in free T index was somewhat steeper than that of total T, owing to a trend for an increase in SHBG with age
LH for gonadal function
It would clearly be better to define the lower limit of normal for a hormone as: the blood level at which metabolic and/or clinical sequelae of hormone deficiency begin to appear, or the level below which definite benefits can be demonstrated for hormone supplementation for a significant proportion of the population
an effect of aging to lower both total and bioavailable circulating T levels at a relatively constant rate, independent of obesity, illness, medications, cigarette smoking, or alcohol intake
Article highlights the problems with the definition of low T. This article finds consistent decline in Total Testosterone and FAI with increasing age groups, with a significant portion of men > 60 meeting the required levels for "low T". This study found a decrease in total T and FAI at a consistent rate independent of variables, such as BMI. This study did find a decrease in SHBG and total T with obesity; in contrast to other studies.
Interesting read: study finds peak Testosterone at age 19 in men; Testosterone decline was see up to age 40 at which decline was variable beyond age 40
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Estrogen receptors alpha and beta show dominance in the proliferative phases, with alpha isoform predominating. In the secretory phase, less expression of ER was present.
ER alpha was predominantly expressed in the epithelial and stromal cells in the proliferative phase. ER beta was predominantly expressed in glandular cells in the same proliferative phase.
in the luteal phase, ER alpha expression declined in the funtionalis layers. ER alpha in the basalis remained unchanged. ER beta in the functionalis layers also declined in the luteal phase.
No relative change was found in the weak expression of ER alpha/beta in the myometrium.
Finnish study of 3,271 men found that there was a decline in serum free testosterone levels in recently born boys compared to previous generations. Additionally, they found inappropriate HPA response to this decline in testicular testosterone.
lower levels of SHBG and serum testosterone were found in more recently born men. Preceding generations of men produced higher testosterone levels than men born in more recent generations.
This study found that in longitudinal studies, testosterone decline accelerated compared to cross sectional studies. They concluded that decreasing health could be the explanation. But, what if the decline in testosterone explained the decreasing health?
Medical dogma tells us that menopause is simply an estrogen deficiency. This new study points to correlation between progesterone decline and cognitive decline in menopausal women.
study finds no correlation between gonadotropin levels, increasing Testosterone levels and homocysteine levels. The treatment group had significant decline in folic acid and B12 after 6 months of treatment and this correlated with the decline in homocysteine.