Endocrine Determinants of Successful Aging in the Male

Summary: A whole bunch of hormone levels go down when men get old

Interestingness: 3

Paper by Annewieke W van den Beld and Steven WJ Lamberts in the Journal of Anti-Aging Medicine, Volume 3, Issue 2, June 2000.

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This is another paper that reads like a review paper, even though they keep referring to their study of 400 73-94 year old men in the Netherlands. Most of what's quoted is about other studies. When they talk about their own study, I'll note it, and I'll mainly focus on their results, not the survey. Their study mostly lacks graphs and numbers, so I'll stick to what they describe it as (increase, decrease, etc).

They "confirm" other studies that say that muscle strength is the major feature that determines whether an old man remains functionally independent.

Mean serum total testosterone (T) in males goes down by about 30% between being 25 and 75. Mean serum free T goes down by 50%. The difference is explained by an increase in sex-hormone-binding globulin (SHBG). In their study they found a correlation between free T and muscle strength, but none between T and life satisfaction.

In their study they see luteinising hormone (LH), which triggers release of T by the testicles, going up with age, and it being inversely correlated with T concentrations. Other studies show mixed results for this relation.

Drop in estradiol (E2) and estrone (E1) with age. In their study, strong correlation between E2 and bone density, and E2 and life satisfaction.

Drop in dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) with age. DHEAS level at 85 is one fifth of level at 30. DHEAS levels in adults > 10 times higher than cortisol (!). In their study, no relation between DHEAS and muscle strength, and relation between DHEAS and bone density disappears when adjusting for T and E1,E2 levels.

And again growth hormone (GH) secretion drops with age, insulin-like growth factor 1 (IGF-1) drops with age, IGF-binding protein 3 (IGFBP-3) drops with age, but IGFBP-2 and IGFBP-1 increase with age. Their study concurs. Also in their study, they didn't see relation between IGF-1 and physical functional status, but did see a strong inverse relation between IGFBP-2 and muscle strength, and they like IGFBP-2 as an indicator of overall level of physical functional status.
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Abstract follows:

Frailty is characterized by generalized weakness, impaired mobility and balance, and poor endurance. Loss of muscle strength is an important factor in the process of frailty, and is the limiting factor for an individual's chances of living an independent life until death. In men, several hormonal systems show a decline in activity during aging. Serum bioavailable testosterone (T) and estradiol (E2), dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), and growth hormone (GH) and insulin-like growth factor (IGF)-I concentrations all decrease during aging in men. Physical changes during aging have been considered physiological, but there is evidence that some of these changes are related to this decline in hormonal activity. Studies on hormone administration in the elderly appear to be promising. However, until now, hormone replacement is not yet proven to beneficial and safe.

Estrogen and Brain Aging

Summary: Description of mostly suggestive data about the effects and importance of estrogen on aging in the brain

Interestingness: 1

Paper by Mahendra K Thakur in the Journal of Anti-Aging Medicine, Volume 2, Issue 2, Summer 1999.


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The most interesting part of the paper is a mention of a result in some other paper that women receiving estrogen replacement therapy (ERT) are 40% less likely to have Alzheimer's disease (AD) than women not receiving ERT.

The rest is a description of the changes in neurotransmitter and receptor densities in the brain as it ages, how estrogen might affect those neurons that produce and receive those neurotransmitters, mainly going by rat studies, results of women's mental scores going down when taking medication that suppresses estrogen production, and how those scores are rescued when taking ERT. I'm not good at absorbing the neurotransmitter information, so I glazed over a lot of it. Nerve growth factor seemed to be mentioned a lot.

There was also mention of estrogen as an antioxidant and its relation to AD. My biases prevailed and I discounted all of it before it even hit my long term memory.
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Abstract follows:

Recent research findings have made it clear that the female sex-steroid hormone estrogen has several functions other than regulation of sexual and reproductive behavior. In addition to this hormone's well-known influence on bone and the heart, this hormone exerts a wide variety of effects on the brain, including both development and function. The current interest in aging of the brain derives, in part, from the enormous and global increase in the proportion of elderly people. Old age is associated with several health problems including a general decline in mental function, especially in dementia, and specifically Alzheimer's dementia (AD). To focus on this issue, it is essential to understand the changes taking place in the aging brain and the role that estrogen plays in this process. This article reviews the data on the involvement of estrogen in the aging brain and discusses the potential consequences of estrogen replacement therapy.
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Hormones and Breast Cancer

Summary: Estrogen replacement hormones cause breast cancer

Interestingness: 2

Paper by Graham A Colditz, MD, Dr.Ph, FAFPHM in the Journal of Anti-Aging Medicine, Volume 1, Issue 4, Winter 1998.

(((This paper is a subset of the previous one, with a few more details. This summary is going to be very short)))

Higher levels of estrogens in postmenopausal women are associated with higher incidence of breast cancer and lower breast cancer survival. In a smallish study, 130 women, risk of breast cancer was 3.2 (1.4-7.0) times higher among postmenopausal women in the highest quartile of estrogen levels compared with those in the lowest. Other studies give similar results. Yet other studies suggest that risk of breast cancer is associated linearly with accumulated cell divisions in breast epithelial cells.

Since women with the lowest levels of postmenopausal estrogen are more likely to get hormone replacement therapy (HRT), the effect of HRT on breast cancer will be partially hidden if not correcting for this factor. Also, because lower age of menopause is associated with a much lower risk of breast cancer, women on HRT have a lower risk of breast cancer than non-users of the same age (((that only makes sense to me if the non-user hasn't undergone menopause, or is it that the effect of later menopause enough to override total accumulated effect of HRT of all practical time spans?))). A large meta-analysis, of a total of 50000 breast cancer cases and 100000 non-breast cancer cases, estimates risk of breast cancer increases 2.3% (1.1-3.6) per year on HRT. Most studies in the meta-analysis were only using estrogens (((but other parts of the paper claim that progestins wouldn't help and might worsen the risk))). From the meta-analysis, they estimated that for every 1000 postmenopausal women who start HRT at 50, six more will get breast cancer if they use it for ten years, and 12 more if they use it for 15.

(((Summary: again, not particularly influential in life expectancy. Also, I think I remember some big study that came up in the last couple of years, maybe 2008, that most likely supercedes anything in the last couple of posts. This is the main reason I gave both these papers a low interestingness rating. The CHD benefits, if I remember correctly, turned out not to be real)))


Abstract follows:

The role of estrogen replacement therapy in the cause of breast cancer continues to be debated. This article reviews the literature on hormones and breast cancer, including articles on cell proliferation, endogenous hormone levels, epidemiologic studies, and the risk of breast cancer. A cause of cancer is defined as a factor that increases the probability that cancer will develop in an individual. A causal relationship between female hormones and breast cancer is consistently suggested by several lines of argument, especially the relationship between duration of use and risk of breast cancer, dose-response with endogenous hormone levels, and biologic plausibility. The magnitude of the increase in risk of breast cancer caused by using hormone replacement is comparable to that seen in delayed menopause. The positive correlation between endogenous hormone levels and risk of breast cancer supports a causal relationship between exogenous hormone use and breast cancer. The increase in risk of breast cancer with increasing duration of use, which does not vary substantially across studies, offers further evidence for a causal relationship. The reduction in mortality rate with short-term use of hormones, although strongest among women with risk factors for cardiovascular disease, adds complexity to the risk-to-benefit trade-off associated with long-term hormone use. All evidence supports a causal relationship between both endogenous estrogens and the use of estrogens and progestins, and breast cancer incidence in postmenopausal women. Hormones act to promote the late stages of carcinogenesis among postmenopausal women and to facilitate proliferation of malignant cells. Strategies for relief of menopausal symptoms and long-term prevention of osteoporosis and heart disease that do not cause breast cancer are urgently needed.

Estrogen Therapy For Menopause

Summary: Review of health benefits and risks of estrogen on post-menopausal women

Interestingness: 2

Paper by Kathryn A Martin MD in the Journal of Anti-Aging Medicine, Volume 1, Issue 4, Winter 1998.

(((This paper is a dense but nicely written review of the effects of estrogen on post-menopausal women. It is hard to summarise since it already is a summary. I'm going to pick out interesting snippets)))

The postmenopausal ovary produces almost no estrogen. Estrogen in postmenopausal women is mainly produced by conversion of androstendedione (((don't know where that happens))). Average age of menopause is 51 (((or was back then, and probably in the USA. Last third of their life spent with assumedly little estrogen, although there is no plot or numbers of levels of estrogen in the paper))).

Some problems associated with this drop in estrogen are vaginal dryness, pain during sex and symptoms similar to urinary tract infection. Hot flushes are also experienced by 75% of women which commonly leads to insomnia and its derivative problems. Osteoporosis is also common, and the risk of coronary heart disease (CHD) goes up by a lot (((doesn't say))). Estrogen in hormone replacement therapy (HRT) helps with the flushes, and the vaginal and urinary tract problems. It also stops the osteoporosis and decreases the risk of CHD (((by 50% it seems from later in the paper))) when given in doses equivalent to 625 micrograms in conjugated form, or equivalent. Although a 15-year study on postmenopausal women did not notice any difference between estrogen and non-estrogen users with respect to cognitive function, a meta-analysis of epidemiological and control studies claims the risk of dementia for estrogen users to be 0.71 (0.53-0.96) compared to non-users (((but the paper abstract discourages that conclusion))).

Five types of HRT are used:

• estrogen only (625 micrograms conjugated)
• cyclic combined: estrogen (625 micrograms conjugated) for days 1-25 of the month, medroxy-progesterone acetate (MPA, a progestin), 5mg, days 13-25. This is the most popular option.
• continuous combined: estrogen (625 micrograms conjugated), and MPA (2.5 mg) without breaks.
• other estrogen preparations: Different variants all equivalent to the 625 micrograms of conjugated estrogen. Some as vaginal creams.
• low dose contraceptives: these are mostly used by women around menopause time

Risks of HRT when supplying only estrogen include increased risks of gallstones, endometrial hyperplasia and cancer (((uterus))), and breast cancer. The increase in uterine cancer can be cancelled by adding in progestin, but it doesn't seem to help with the breast cancer. Breast cancer risk is a factor of 1.35 (1.21-1.49) compared to baseline after 5 years of HRT.

Estrogen raises high density lipoprotein (HDL) and decreases low-density lipoprotein (LDL), but progestin has the opposite effect (((although it later says that women under the combined therapy had HDL levels similar to women only taking estrogen, and that the protective effects against CHD were similar in both groups))). Estrogen suppresses platelet function and is a potent vasodilator. It also improved 10-year survival of women with narrowing of their coronary arteries. On a different study though, HRT did not improve survival of women with CHD and risk of events (((heart attacks?))) was higher during the first year compared to placebo.

Some new substances can act as estrogen agonists in some tissue and estrogen antagonists in others. Raloxifene, for example, appeared, in one study, to have an estrogen agonist effect with respect to osteoporosis and lipid profile, but antagonist with respect to breast and endometrial tissue. Even though it affected lipids in a positive way, it did not show improvement with respect to artherosclerosis.

(((Summary: I don't think it'd have a major effect on longevity)))

Abstract follows:

The medical management of menopause continues to be a topic of controversy. Although many of the benefits of estrogen therapy have been well established (treatment of estrogendeficiency symptoms, prevention of osteoporosis, and prevention of coronary heart disease), the potential risks of breast cancer are of great concern. Although many postmenopausal women are candidates for hormone replacement therapy (HRT), many choose not to take it because of fear of breast cancer or concerns about potential side effects and continued menstrual bleeding. Therefore, making choices about potential therapies after menopause can be a difficult one for both women and their health care providers. An important principle of HRT is the notion of short-term versus long-term use, as the goals of both therapy and riskbenefit profiles are different. Although most perimenopausal and postmenopausal women are candidates for short-term HRT (with the exception of those with a history of breast cancer), no general consensus is found regarding who should or should not receive long-term HRT. Other new areas of clinical investigation in the field of menopause and HRT include the possible impact of estrogen on cognitive function, the role of exogenous androgen replacement for libido, and the role of a new class of drugs known as "selective estrogen receptor modulators" (SERMs). Given this rapidly changing field, it is likely that the medical management of menopause will continue to evolve in the coming years.