Longevity and Sex Hormones
There are hundreds
of journal articles demonstrating the health-longevity benefits of estradiol. The main mechanism by which women extend life with HRT, and conversely die sooner with less estradiol is through estradiol
promoting anti-oxidant production, which thus lowers the risk of numerous chronic age related conditions. Others positive effects from HRT include bone remodeling which prevents osteoporosis, mild androgen affect
through conversion of about 10% to testosterone, which prevents sarcopenia prevent loss of muscle, anti-inflammatory effect
for reduction of risk of rheumatoid arthritis. The greatest life extension comes
through the prevention of cardiovascular disease, which comes mainly through the anti-oxidation and down regulating the immune
response and thereby reducing atherogenesis and thus cardiovascular disease. For
a complete list of benefits, why pharma’s HRT are significantly inferior to natural HRT, the junk science used staring
in the late 90s by pharma to limit HRT usage, and recommendation for natural HRT go to http://healthfully.org/rc/id2.html .
There are hundreds
of journal articles demonstrating the longevity for testosterone supplement, though a number for its health benefits. The association is weak because the research has been done. HRT
for women has been widely marketed for decades because the progestin added entail that the product was patentable. With Testosterone that approach to market never met success.
In the 1980 Goodman and Gilman pharmacology textbook, page 1456-8 are listed 18 analogues of testosterone, none of
them have every been widely used. However, for testosterone, given that it has
just one functional group difference for that of estrogen, and given that many of the health benefits, a reasonable conclusion
is that there are significant health benefits that promote longevity. Moreover,
given that those in the lowest 20% (quintile) have a mortality rate twice that of the highest quintile, this confirms the
hypothesis (note: those in the lowest quintile have a much higher percentage of people with major health issues including
diabetes, cancer, cancer, etc. for which some cause low testosterone.) For
benefits of testosterone supplement, response to pharma’s junk science, and recommendations go to http://healthfully.org/rc/id7.html.
http://sageke.sciencemag.org/cgi/content/abstract/2005/23/pe17 , Science of Aging, June 8, 2005
Why Females Live Longer
Than Males: Control of Longevity by Sex Hormones
Abstract: Females live longer than males in many species, including humans. We have traced a possible explanation for
this phenomenon to the beneficial action of estrogens, which bind to estrogen receptors and increase the expression of longevity-associated
genes, including those encoding the antioxidant enzymes superoxide dismutase and glutathione peroxidase. As a result, mitochondria
from females produce fewer reactive oxygen species than those from males. Administering estrogens has serious drawbacks, however--they
are feminizing (and thus cannot be administered to males) and may increase the incidence of serious diseases such as uterine
cancer in postmenopausal women. Phytoestrogens, which are present in soy or wine, may have some of the favorable effects of
estrogens without their undesirable effects. Study of gender differences in longevity may help us to understand the basic
processes of aging and to devise practical strategies to increase the longevity of both females and males.
Shows that estrogen down regulates insulin and reduces
oxidative stress in female mice.
Estrogen, Insulin, and
Dietary Signals Cooperatively Regulate Longevity Signals to Enhance Resistance to Oxidative Stress in Mice--2005
[Partial abstract] Suggesting that the suppressed insulin signaling leads to an enhanced antioxidant
defense. It was found that the survival of mice under 80% oxygen [oxidative
stress via high air oxygen] was extended when they were administered estradiol. In contrast, mutant and wild-type female mice
showed shortened survivals when their ovaries were removed. The influence of
estrogen is remarkable in mutant mice compared with wild-type mice, suggesting that estrogen modulates insulin signaling in
mutant mice. Furthermore, we showed additional extension of survival under oxidative
conditions when their diet was restricted. Collectively, we show that three distinct signals; insulin, estrogen, and dietary
signals work in independent and cooperative ways to enhance the resistance to oxidative stress in mice.
There are major issue with a population study. These include too low a dose, estrogen mimic instead of estrogen, using a different
estrogen estriol which is an antagonist (blocks) of estradiol, and using it with a progestin such as medroxyprogesterone which
also blocks some of the beneficial effects of estradiol. Finally many of the
women used equine (horse estrogen) which is of unknown value (the 625 mg. is the commonly used horse estrogen dose). Nevertheless there was modest benefit. In
a similar Danish study using Nordisc survival was with long-term usage (over 10 years) extended life 4 years.
Menopause. 2006 Jan-Feb; 13(1): 12–18. doi: 10.1097/01.gme.0000172880.40831.3b
Increased longevity in older users of postmenopausal
estrogen therapy: the Leisure World Cohort Study--2006
To examine the effect of postmenopausal estrogen therapy (ET), including duration and recency of use, on all-cause
mortality in older women.
As part of a prospective cohort study of residents of a California retirement community begun in the early 1980s,
Leisure World Cohort women (median age, 73 y) completed a postal health survey including details on ETuse and were followed
up for 22 years (1981–2003). Age- and multivariate-adjusted risk ratios (RR) and 95% CIs were calculated using proportional
Of the 8,801 women, 6,626 died during follow-up (median age, 88 y). ET users had an age-adjusted mortality rate of
52.9 per 1,000 person-years compared with 56.5 among lifetime nonusers (RR = 0.91; 95% CI, 0.87–0.96). Risk of death decreased with both increasing duration of ET and decreasing years since last
use (P for trend <0.001).
The risk was lowest among long-term (≥15 y)
users (RR = 0.83; 95% CI, 0.74–0.93 for 15–19 y and RR = 0.87; 95% CI, 0.80–0.94
for 20+ y). For long-term users, the age-adjusted mortality rate was 50.4 per 1,000 person-years. Lower-dose users (≤0.625
mg) had a slightly better survival rate than higher-dose users (RR = 0.84; 95% CI, 0.78–0.91 vs RR = 0.91; 95% CI, 0.83–0.97).
[This is because Prempro, horse estrogen with MPA, is in the high dose group].
Risk did not differ by route of administration (P = 0.56). Further adjustment for potential confounders had little effect on the observed RRs for ET.
Long-term ET is associated with lower all-cause mortality in older women.
Full http://www.sciencedirect.com/science/article/pii/S0014579305004540 doi:10.1016/j.febslet.2005.03.090
Why females live longer than males? Importance
of the upregulation of longevity-associated genes by oestrogenic compounds--2005
Females live longer than males in many mammalian species, including humans.
Mitochondria from females produce approximately half the amount of H2O2 than
males. We have found that females behave as double transgenics overexpressing both superoxide dismutase and glutathione peroxidase.
This is due to oestrogens that act by binding to the estrogen receptors and subsequently
activating the mitogen activated protein (MAP) kinase and nuclear factor kappa B (NF-κB) signalling pathways. [Some]
Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of upregulating
antioxidant genes, by hormonal and dietary manipulations, in order to increase longevity is discussed.
J Gerontol A Biol Sci Med Sci(2012)doi: 10.1093/gerona/gls068
The Role of Androgens and Estrogens on Healthy Aging
Aging is associated with a loss of sex hormone in both
men (andropause) and women (menopause). In men, reductions in testosterone can trigger declines in muscle mass, bone mass,
and in physical function. In women, the impact of the loss of sex hormones, such as estradiol, on bone is well elucidated,
but evidence is limited on whether the loss of estradiol negatively affects muscle mass and physical function. However, deficiencies
in multiple anabolic hormones have been shown to predict health status and longevity in older persons. Thus, consideration
should be given as to whether targeted hormone replacement therapies may prove effective at treating clinical conditions,
such as age-related sarcopenia, cancer cachexia, and/or acute or chronic illnesses. If initiated carefully in the appropriate
clinical population, hormone replacement therapies in men and women may prevent and reverse muscle and bone loss and functional
declines and perhaps promote healthy aging and longevity.