Category Archives: Bio-Identical Hormones

Middle Aged Men, Too, Can Blame Estrogen for That Waistline

It is the scourge of many a middle-aged man: he starts getting a pot belly, using lighter weights at the gym and somehow just doesn’t have the sexual desire of his younger years.

The obvious culprit is testosterone, since men gradually make less of the male sex hormone as years go by. But a surprising new answer is emerging, one that doctors say could reinvigorate the study of how men’s bodies age. Estrogen, the female sex hormone, turns out to play a much bigger role in men’s bodies than previously thought, and falling levels contribute to their expanding waistlines just as they do in women’s.

The discovery of the role of estrogen in men is “a major advance,” said Dr. Peter J. Snyder, a professor of medicine at the University of Pennsylvania, who is leading a big new research project on hormone therapy for men 65 and over. Until recently, testosterone deficiency was considered nearly the sole reason that men undergo the familiar physical complaints of midlife.

The new frontier of research involves figuring out which hormone does what in men, and how body functions are affected at different hormone levels. While dwindling testosterone levels are to blame for middle-aged men’s smaller muscles, falling levels of estrogen regulate fat accumulation, according to a study published Wednesday in The New England Journal of Medicine, which provided the most conclusive evidence to date that estrogen is a major factor in male midlife woes. And both hormones are needed for libido.

“Some of the symptoms routinely attributed to testosterone deficiency are actually partially or almost exclusively caused by the decline in estrogens,” said Dr. Joel Finkelstein, an endocrinologist at Harvard Medical School and the study’s lead author, in a news release on Wednesday.

His study is only the start of what many hope will be a new understanding of testosterone and estrogen in men. Dr. Snyder is leading another study, the Testosterone Trial, which measures levels of both hormones and asks whether testosterone treatment can make older men with low testosterone levels more youthful — by letting them walk more quickly, feel more vigorous, improve their sexual functioning and their memories, and strengthen their bones. Smaller studies have been promising but unreliable, and estrogen has not been factored in.

“We had ignored this hormone in men, but we are studying it now,” said Dr. Alvin M. Matsumoto, a testosterone and geriatrics researcher at the University of Washington School of Medicine and the V.A. Puget Sound Health Care System, who is a Testosterone Trial researcher. “We are just starting out on this road.”

Both men and women make estrogen out of testosterone, and men make so much that they end up with at least twice as much estrogen as postmenopausal women. As levels of both hormones decline with age, the body changes. But until now, researchers have focused almost exclusively on how estrogen affects women and how testosterone affects men.

Dr. Finkelstein’s study provides a new road map of the function of each hormone and its behavior at various levels. It suggests that different symptoms kick in at different levels of testosterone deficiency. Testosterone, he found, is the chief regulator of muscle tone and lean body mass, but it takes less than was thought to maintain muscle. For a young man, 550 nanograms of testosterone per deciliter of blood serum is the average level, and doctors have generally considered levels below 300 nanograms so low they might require treatment, typically with testosterone gels.

But Dr. Finkelstein’s study found that muscle strength and size turn out to be unaffected until testosterone levels drop very low, below 200 nanograms. Fat accumulation, however, kicks in at higher testosterone levels: at 300 to 350 nanograms of testosterone, estrogen levels sink low enough that middle-aged spread begins.

As for sexual desire and performance, both require estrogen and testosterone, and they increase steadily as those hormone levels rise. Researchers say it is too early to make many specific recommendations, but no one is suggesting that men take estrogen, because high doses cause feminine features like enlarged breasts.

Although doctors prescribe testosterone gels for men whose levels fall below 300 nanograms per deciliter, that cutoff point is arbitrary, and there is no clinical rationale for it, Dr. Finkelstein said. Often men take the hormone to treat complaints like fatigue, depression or loss of sexual desire, which may or may not be from low levels of testosterone. The data suggest that men with levels around 300 nanograms who complain of sexual problems may want to try testosterone, but those who complain of flagging muscle strength should not blame testosterone deficiency, Dr. Finkelstein said. But, he added, “symptoms of low testosterone tend to be quite vague.”

Today, millions of men are using testosterone gels, fueling a nearly $2 billion market.

For their study, Dr. Finkelstein and his colleagues recruited 400 men aged 20 to 50 who agreed to have their testosterone production turned off for 16 weeks. Half then received varying amounts of

It turned out to be surprisingly easy to recruit subjects, Dr. Finkelstein said. One, Ben Iverson, joined in part for the $1,000 subjects were paid. “That, to me, was enticing,” he said. He was a 28-year-old Harvard graduate student at the time and is now an assistant professor of finance at Northwestern University.

Although Mr. Iverson’s wife looked askance at the injections to block testosterone production, Mr. Iverson ended up getting enough testosterone in the gel he was assigned to use. The worst were the testosterone-suppressing injections, which required him to use a huge needle in his abdomen once a month, he said.

He found out when the study ended that he was in a group that got enough testosterone to keep his levels in a normal range. “I literally did not notice any difference at all,” Mr. Iverson recalled.

The worst symptoms were in men whose estrogen production was shut down — they got intense hot flashes.

Now Dr. Finkelstein is repeating the study with older men. The Testosterone Trial is looking at them too.

For that study, Dr. Snyder and his colleagues recruited nearly 800 men aged 65 and older who have low testosterone levels. The men take either a placebo or enough testosterone to bring their level to between 400 and 800. Investigators are assessing walking speed, sexual functioning, vitality, memory, red-blood-cell count, bones and coronary arteries. The yearlong study will be completed next year.

Next, researchers said, they want to do a large study like one conducted with thousands of women in 2002 that asked about long-term risks and benefits of hormone therapy. Does testosterone therapy lead, for example, to more prostate cancer? Does it prevent heart attacks?

“We still don’t know the answers to the clinical questions,” Dr. Matsumoto said. “Does it prevent things that are really important?”

By GINA KOLATA, Published: September 11, 2013, source: http://www.nytimes.com/2013/09/12/science/middle-aged-men-can-blame-estrogen-too.html

Higher circulating levels of IGF-1 are associated with longer leukocyte telomere length in healthy subjects.

Brimacombe M, Nawrot TS,§tgessen JA, Pollak l\/N, Aviv A.
Department of Geriatric Medicine and Metabolic Diseases, Second University of Naples, Piazza
Miraglia 2, 80138 Naples, Italy.
Abstract
Nbtations that inhibit the insulin-like growth factor-1 (IGF-1) extend the lifespan of worms, flies and mice. However, it appears that relatively low circulating levels oflGF-1 in humans are associated with aging- related diseases and diminished longevity. As leukocyte telomere length (l_TL) is ostensibly a biomarker of human aging, we examined the relationship between LTl_ and blood IGF-1 in a healthy cohort. Our sample comprised 476 healthy, unrelated Caucasians (208 men and 268 women), aged 16-104 years, living in the West Coast of Southem Italy. We measured L’l’L by Southem blots and IGF-1 by enzyme- linked immunoassay. Both IGF-1 and LTl_ diminished with age (lGF-1, |=-0.601, P<0.001; LTl_, r=-0.706, P<0.001). Continue reading

Hgh sand Alzheimer’s IGF-1 Deficiency Possible Contributor to Alzheimer’s in Men

From: Andrea
Date: December 1, 2012 9:16:55 AM PST
To: colerai4b@hpeprint.com
Subject: Hgh sand Alzheimer’s
IGF-1 Deficiency Possible Contributor to Alzheimer’s in Men Journal of Clinical Endocrinology & Metabolism reports that low levels of Insulin Like Growlh Factor linked to Alzheimer’s in men but not in women. Continue reading

The lGF-1IlGF-1R signaling axis in the skin

The lGF-1IlGF-1R signaling axis in the skin: a new role for the dermis in aging-associated skin cancer.
Lewis DA, Travers JB, Somani AK, .
Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Abstract
The appropriate response of human keratinocytes to ultraviolet-B (UVB) is dependent on the activation status of the insulin-like growth factor 1 (lGF-1) receptor. Keratinocytes Ql’OWfl in conditions in which the IGF-1 receptor is inactive inappropriately replicate in the presence of UVB-induced DNA damage. Continue reading

A Randomized, Placebo-Controlled Trial

Howard B.A. Baum, MD; Beverly M.K. Biller, MD; Joel S. Finkelstein, MD;
Kristin Baker Cannistraro, BS, RN; Daniel S. Oppenheim, MD, PhD; David A. Schoenfeld, PhD; Theresa
Hoskins Michel, PT, MS; Harriet Wittink, PT, MS; and Anne Klibanski, MD
‘ Background: Patients with adultonset growth hormone deficiency have reduced bone density and increased fat mass. Growth hormone at high doses may decrease body fat in these patients, but the effects of growth hormone at more physiologic doses on bone density and body compo- sifion have not been convincingly shown.
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Higher circulating levels of IGF-1 are associated with longer leukocyte telomere length in healthy subjects.

Sent from my iPadMech Ageing Dev. 2009 NovDec;130(1 1-12):771-6.
Higher circulating levels of IGF-1 are associated with longer leukocyte telomere length in healthy
subjects.

_l$_, Brimacombe M, Nawrot TS,§tgessen JA, Pollak l\/N, Aviv A.
Department of Geriatric Medicine and Metabolic Diseases, Second University of Naples, Piazza
Miraglia 2, 80138 Naples, Italy.
Abstract
Nbtations that inhibit the insulin-like growth factor-1 (IGF-1) extend the lifespan of worms, flies and mice. However, it appears that relatively low circulating levels oflGF-1 in humans are associated with aging- related diseases and diminished longevity. As leukocyte telomere length (l_TL) is ostensibly a biomarker of human aging, we examined the relationship between LTl_ and blood IGF-1 in a healthy cohort. Our sample comprised 476 healthy, unrelated Caucasians (208 men and 268 women), aged 16-104 years, living in the West Coast of Southern Italy. Continue reading

Growth hormone releasing hormone improves the cognition of healthy older adults.

Neurobiol Agigg. 2006 Feb;27(2):318-23. Epub 2005 Mar 23.

Vitiello MV, Moe KE, Merriam GR, Mazzoni G, Buchner DH, Schwartz RS.
Department of Psychiatry and Behavioral Sciences, BB-1520D Health Science Building, University of Washington, Box 356560, 1959 NE Pacific Street, Seattle, WA 98195-6560, USA. vitielIo@u.washington.edu
Abstract
Declines in the activity of the somatotrophic axis have been implicated in the age-related changes observed in a number of physiological functions, including cognition. Continue reading

Reduced telomerase activity in human T lymphocytes exposed to cortisol

Jenny Choi, Steven R. Fauce, and Rita B. Effros
Author information ► Copyright and License information ►
The publisher’s final edited version of this article is available at Brain Behav Immun
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Abstract

Accelerated telomere shortening in lymphocytes has been associated with a variety of human pathologies, including HIV disease, Down syndrome, and cardiovascular disease. Recent findings indicate that reduced telomere length is also associated with chronic psychological stress and mood disorders. Telomerase, which prevents telomere shortening, can be upregulated in T lymphocytes in concert with activation, thereby retarding telomere shortening. Here, we demonstrate that exposure of human T lymphocytes to cortisol is associated with a significant reduction in telomerase activity both during primary stimulation of resting cells and secondary stimulation of previously activated cells. The effect is observed in both CD4 and CD8 T lymphocytes, and is associated with reduced transcription of hTERT, the telomerase catalytic component. These findings provide a potential mechanism for stress-associated telomere length attrition, and suggest that strategies to enhance T lymphocyte telomerase activity may provide beneficial effects on immune function in situations of chronic emotional stress.

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Measures of submaximal aerobic performance evaluate and predict functional response to growth hormone (GH) treatment in GH-deficient adults.

Woodhouse LJ, Asa SL, Thomas SG, Ezzat S.

Department of Physical Therapy, The University of Toronto, Ontario, Canada.

The impact of GH on functional performance in GH-deficient adults is not well understood. To investigate the effects of GH on skeletal muscle, physical, and functional capacity, we randomized 28 GH-deficient adults to receive 3 months of recombinant human GH [rhGH: somatotropin, 6.25 microg/kg lean body mass (LBM) for 1 month, 12.5 microg/kg LBM thereafter] in a double-blind placebo-controlled crossover trial. We measured muscle fiber type, size, and insulin-like growth factor I messenger RNA, aerobic capacity [maximal oxygen uptake (VO2max), ventilation threshold (VeT)], isokinetic strength, oxygen-cost-of-walking at normal and fast speeds, and fatigue determined by the profile of mood states questionnaire. Continue reading